Research

Most healthy individuals have a propensity to develop autoimmune diseases, as evidenced by the presence of autoreactive T cells in their naïve periphery. T cells are educated in the thymus, where high-affinity T cell receptor (TCR)-bearing cells that interact with self-antigens are deleted by negative selection, while T cells with low-affinity TCR to self-antigens are selected positively and exported to the periphery. In spite of the presence of self-reactive T cells in the naïve peripheral repertoires, autoimmune responses do not ensue spontaneously. How this tolerance is maintained is a fundamental question. It has been suggested that the environmental antigens that bear similarities to self-antigens break self-tolerance by cross-reactivity. To this end, we focus our investigations on the identification of microbial products that can potentially induce autoimmunity in the heart and immunologically privileged sites such as the central nervous system and eyes through antigenic mimicry. Mechanistically, we are particularly interested in delineating the role of antigen-specific T cells in the autoimmune diseases of infectious origin.

DISEASE MODELS

Myocarditis/heart autoimmunity
1. Experimental autoimmune myocarditis.
  Using cardiac myosin heavy chain (Myhc)-α 334-352 as a cardiac autoantigen, we recently discovered a novel bacterium called Bacillus infantis NRRL B-14911 that has the potential to induce autoimmune myocarditis in A/J mice through antigenic mimicry. Our data support the notion that exposure to environmental microbes, which are otherwise innocuous, can predispose to the development of myocardial damage in genetically susceptible individuals. We are currently investigating the pathogenic attributes of Bacillus infantis in the mediation of infectious myocarditis.
  
  Additional information:
  
  http://www.sciencedirect.com/science/article/pii/S0008874911002140
2. Coxsackievirus B3 (CVB3)-induced myocarditis.
  Using CVB3 as a bona fide pathogen of the cardiovascular system, we addressed the long-standing question whether chronic myocarditis that occurs in CVB3 infection is due to an autoimmune response to cardiac antigens. Using myocarditis-susceptible A/J mice, we demonstrated that animals infected with CVB3 show the generation of Myhc-α-specific CD4 T cells that can transfer the disease to naïve recipients. We suggest that pathogens like CVB3 that primarily infect hearts can lead to secondary generation of pathogenic autoimmune responses resulting from release of self-antigens due to cardiac injury. We propose that the immune-mediated damage is superimposed on the initial tissue destruction caused by the virus, but once autoimmune response sets in, the disease process becomes perpetual, leading to the development of chronic myocarditis/dilated cardiomyopathy. We are now delineating these events.
  Additional information:
  
  http://www.sciencedirect.com/science/article/pii/S1521661612001660
Multiple sclerosis (MS) / central nervous system (CNS) autoimmunity
1. Experimental autoimmune encephalomyelitis (EAE).
  EAE models have been traditionally used to address the immune events in the pathogenesis of multiple sclerosis (MS). We focus on two models: EAE induced with myelin proteolipid protein (PLP) 139-151 and EAE induced with myelin oligodendrocyte glycoprotein (MOG) 35-55, in SJL and C57Bl/6 mice, respectively. Using PLP 139-151 as a model antigen, we discovered that Acanthamoeba castellaniicastellanii has the potential to trigger MS by generating cross-reactive T cells for two well-characterized myelin antigens, PLP 139-151 and myelin basic protein 85-99. Our preliminary results suggest that MS patients, but not patients with other neurological disorders, show evidence of Acanthamoeba-genomic material in their cerebrospinal fluids.
  
  Additional information:
  
  http://www.sciencedirect.com/science/article/pii/S0165572809004688
  http://www.sciencedirect.com/science/article/pii/S0165572810004303#
  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098506
2. Role of reactive oxygen species in self-tolerance and autoimmunity.
  The general dogma is that increased reactive oxygen species (ROS) production is detrimental and causes tissue injuries. However, this paradigm has been recently revisited with an observation that oxidative burst in fact is beneficial in controlling autoimmune responses. To directly address the role of ROS in the mediation of CNS autoimmunity, we used mice deficient for copper-zinc superoxide dismutase (SOD1), an endogenous regulator of ROS. SOD1-deficient C57Bl/6 mice were found to develop more severe EAE induced with MOG 35-55 as compared with their littermate wild type controls. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather, lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance of self-tolerance leading to the suppression of autoimmune responses.
  
  Additional information:
  
  http://www.sciencedirect.com/science/article/pii/S0165572812003372
  
  In addition, to dissect the complex nature of ROS-mediated effects in immune cells, we made efforts to characterize microRNAs (miRNAs) that are responsive to oxidative stress, leading us to identify a set of miRNAs to be uniquely expressed in response to hydrogen peroxide in the mouse macrophage cell line, RAW 264.7. One of these, miR-27b*, has a modulating effect on nuclear factor-kB activation, suggesting a role for oxidative stress-responsive miRNAs in modulating the innate immune functions.
  
  Additional information:
  
  http://link.springer.com/article/10.1007%2Fs11010-011-0752-2
3. Urinary metabolites as biomarkers of CNS autoimmunity.
  Using fingolimod as a disease-modifying agent in MOG 35-55-induced EAE, we made efforts to identify the urinary metabolites that are indicative of disease progression and to monitor response to therapy. NMR analysis of metabolites allowed us to distinguish EAE from healthy mice and from those treated with or without fingolimod, suggesting that urinary metabolites have significant promise for assessing CNS autoimmunity. Efforts are under way to investigate the urinary metabolites in a clinical cohort study involving patients with MS and other neurological diseases.
  
  Additional information:
  
  http://pubs.acs.org/doi/abs/10.1021/cb300673e
Uveitis/uveoretinitis
Experimental autoimmune uveoretinitis (EAU).
To identify the infectious triggers of uveitis and their underlying mechanisms, we established an EAU model induced with interphotoreceptor retinoid-binding protein (IRBP) 201-216 in A/J mice. Our focus is to identify pathogens primarily affecting the eyes with an expectation that such microbes can serve as ideal candidates to delineate the autoimmune events of uveitic conditions. We discovered that although one mimicry epitope derived from Ehrlichia canis could induce IRBP-specific T cells, it failed to induce EAU. Rather, the mimicry epitope prevented the disease induced with IRBP 201-216 by acting as a naturally occurring altered peptide ligand. We theorize that in typical host-parasite relationships, microbes carrying mimicry epitopes can induce pathogenic cross-reactive immune responses, which may result in the death of the host. Such outcomes are not favorable for survival of parasites. Alternatively, from an evolutionary point of view, it may be possible that as a parasite coexists with a host, it can acquire the host’s genetic material; introduction of mutations under selection pressure, if any, may favor attenuation of the host’s immune response, leading to the parasite’s survival.

Additional information:

http://www.sciencedirect.com/science/article/pii/S0165572813002154

CUTTING-EDGE TECHNIQUES

Major histocompatibility complex (MHC) class II tetramers and dextramers.
1. Detection of antigen-specific CD4 T cells by flow cytometry.
  To determine the precursor frequencies and functionalities of antigen-specific, autoreactive CD4 T cells in various autoimmune disease models, we have generated a series of MHC class II tetramers and/or dextramers as noted below.
  
  Abbreviations: Myhc, cardiac myosin heavy chain; RNase, ribonuclease; IRBP, interphotoreceptor retinoid-binding protein; BAC, Bacillus infantis; PLP, myelin proteolipid protein; ACA, Acanthamoeba castellanii; TMEV, Theiler’s murine encephalomyelitis virus; MOG, myelin oligodendrocyte glycoprotein.
  Additional information:
  
  http://bmcimmunol.biomedcentral.com/articles/10.1186/1471-2172-12-40
2. Detection of antigen-specific CD4 T cells in situ by confocal microscopy.
  We recently established a comprehensive method that permits us to enumerate the frequencies of antigen-specific, autoreactive CD4 T cells in situ in fresh tissues by direct staining without having to amplify the fluorescent signals, an approach commonly employed with conventional MHC tetramers. In particular, staining with dextramers is a one-step reaction, and the whole procedure, from tissue sectioning to staining, can be finished in less than a day.
  Additional information:
  
  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087519
  http://www.jove.com/video/51679/in-situ-detection-autoreactive-cd4-t-cells-brain-heart-using-major
Magnetic resonance microscopy (MRM) imaging of heart in the mouse.
To evaluate cardiac abnormalities in animals affected with myocarditis non-invasively, we have established a MRM imaging technique using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. The technique allows us to ascertain the thickness of the ventricular wall and functional changes in inflamed hearts, such as end diastolic and ejection fractions. Thus, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents such as coxsackievirus B3, as well as response to therapies.
Additional information:

http://www.jove.com/video/51654/noninvasive-assessment-cardiac-abnormalities-experimental-autoimmune

PUBLICATIONS

Research articles

Researcher ID: http://www.researcherid.com/rid/K-7200-2014
ORCID ID: http://orcid.org/0000-0003-4082-9254

Reddy J, Wilkie BN, and Mallard BA. Construction of an internal control to quantitate multiple porcine cytokine mRNAs by RT-PCR. 1996. BioTechniques 21: 868-875. PMID: 8922628
Reddy J, Wilkie BN. Quantitation of porcine cytokine and beta 2-microglobulin mRNA expression by reverse transcription polymerase chain reaction. 2000. J. Immunol. Methods. 233(1-2):83-93. PMID: 10648859.
Reddy J, Borgs P, Wilkie BN. Cytokine mRNA expression in leukocytes of efferent lymph from stimulated lymph nodes in pigs. 2000. Vet. Immunol. Immunopathol. 74(1-2):31-46. PMID: 10760388.
Reddy J, Wilkie BN, Borgs P, and Mallard BA. Cytokines in Mycoplasma hyorhinis-induced arthritis in pigs bred selectively for high and low immune response. 2000. Infect. Immun. 68: 1150-1155. PMID: 10678919.
Reddy J, Chastagner P, Fiette L, Liu X, and Theze J. IL-2-induced TNF-β expression: Further analysis in the IL-2 knockout model and comparison with TNF-, LT-, TNFR1 and TNFR2 modulation. 2001. Int. Immunol. 13: 135-147. PMID: 11157847.
Chastagner P, Reddy J, and Theze J. Lymphoadenopathy in IL-2-Deficient Mice: Further Characterization and overexpression of the antiapoptotic molecule cellular FLIP. 2002. J. Immunol. 169: 3644. PMID: 12244156.
Reddy J, Bettelli E, Nicholson L, Jang M, Wucherpfennig K, and Kuchroo V. Detection of autoreactive myelin proteolipid Protein 139-151-specific T cells by using MHC II IA^s tetramers. 2003., J. Immunol. 170: 870-877. PMID: 12517952.
Reddy J, Illes Z, Zhang X, Encinas J, Pyrdol J, Nicholson L, Sobel RA, Wucherpfennig KW, and Kuchroo VK. Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. 2004. Proc. Natl. Acad. Sci. U S A. 101(43): 15434-9. PMID: 15492218.
Zhang X,. Koldzic DN, Izikson L, Reddy J, Nazareno RF, Sakaguchi S, Kuchroo VK, and Weiner HL. IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD4+CD25+ regulatory T cells. 2004. Int. Immunol. 16: 249-256. PMID: 14734610.
Illes Z, Stern JN, Reddy J, Waldner H, Mycko MP, Brosnan CF, Ellmerich S, Altmann DM, Santambrogio L, Strominger JL, and Kuchroo VK. Modified amino acid copolymers suppress myelin basic protein 85-99-induced encephalomyelitis in humanized mice through different effects on T cells. 2004. Proc. Natl. Acad. Sci. U S A. 101:11749-54. PMID: 15292513.
Stern JN, Illes Z, Reddy J, Keskin DB, Sheu E, Fridkis-Hareli M, Nishimura H, Brosnan CF, Santambrogio L, Kuchroo VK, and Strominger JL. Amelioration of proteolipid protein 139-151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms. 2004. Proc. Natl. Acad. Sci. U S A. 101(32): 11743-8. PMID: 15292514.
Anderson AC, Reddy J (co-first authors), Nazareno R, Sobel RA, Nicholson LB, and Kuchroo VK. IL-10 plays an important role in the homeostatic regulation of the autoreactive repertoire in naive mice. 2004. J. Immunol. 173: 828-834. PMID: 15240669.
Greve B, Reddy J, Waldner HP, Sobel RA, and Kuchroo VK. Dissimilar background genes control susceptibility to autoimmune disease in the context of different MHC haplotypes: NOD.H-2(s) congenic mice are relatively resistant to both experimental autoimmune encephalomyelitis and type I diabetes. 2004. Eur. J. Immunol. 34:1828-1838. PMID: 15214031.
Reddy J, Waldner H, Zhang X, Illes Z, Wucherpfennig KW, Sobel RA, and Kuchroo VK. CD4⁺CD25⁺ regulatory T cells contribute to gender differences in susceptibility to experimental autoimmune encephalomyelitis. 2005. J. Immunol. (cutting edge) 175: 5591-5595. PMID: 16237044
Stern JN, Illes Z, Reddy J (co-first authors), Keskin DB, Sheu E, Fridkis-Hareli M, Kuchroo VK, and Strominger JL. Peptide 15-mers of defined sequence that substitute for random amino acid copolymers in amelioration of experimental autoimmune encephalomyelitis. 2005. Proc. Natl. Acad. Sci. U S A. 102(5): 1620-5. PMID: 15665083.
Illes Z, Waldner H, Reddy J, Bettelli E, Nicholson L, and Kuchroo V. T cell tolerance induced by cross-reactive TCR ligands can be broken by superagonist ligand resulting in anti-inflammatory cytokine production. 2005. J. Immunol. 175: 1491-1497. PMID: 16034086.
Dardalhon V, Schubart, A, Reddy J, Meyers J, Monney L, Sabatos C, Ahuja R, Nguyen K, Freeman G, Greenfield E, Sobel R, and Kuchroo V. CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. 2005. J. Immunol. 175: 1558-1565. PMID: 16034094.
Illes Z, Stern J, Keskin D, Reddy J, Brosnan C, Waldner H, Santambrogio L, Kuchroo V, and Strominger J. Copolymer effects on microglia and T cells in the central nervous system of humanized mice. 2005. Eur. J. Immunol. 35: 3683-93. PMID: 16259003.
Greenfield E, Reddy J, Lees A, Dyer C, Koul O, Nguyen K, Bell S, Kassan N, Hinojoza J, Eaton M, Lees M, Kuchroo V, and Sobel R. Monoclonal Antibodies to Distinct Regions of Human Myelin Proteolipid Protein recognize central nervous system myelin and neurons of many vertebrate species. 2006. J. Neurosci. Res. 83: 415-31. PMID: 16416423.
Zhang X, Reddy J, Ochi H, Frenkel D, Kuchroo V, and Weiner H. Foxp3 expressing CD4+CD25+ regulatory T cells mediate recovery from experimental autoimmune encephalomyelitis. 2006. Int. Immunol. 18: 495-503. PMID: 16540527.
Illes Z, Waldner H, Reddy J, Anderson AC, Sobel RA, and Kuchroo VK. Modulation of CD4 co-receptor limits spontaneous autoimmunity when high-affinity transgenic TCR specific for self-antigen is expressed on a genetically resistant background. 2007. Int. Immunol. 19 (10): 1235-48. PMID: 17804690.
Xiao S, Najafian N, Reddy J, Albin M, Zhu C, Jensen E, Korn T, Anderson AC, Zhang Z, Gutierrez C, Moll T, Sobel R, Umetsu D, Yagita H, Akiba H, Sayegh M, DeKruyff R, Khoury S, and Kuchroo V. Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function. 2007. J. Exp. Med. 204: 1691-702. PMID: 17606630.
Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen T, Bäckström B, Wucherpfennig K, Strom T, Oukka M, and Kuchroo V. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. 2007. Nat. Med. 4: 423-31. PMID: 17384649.
Elyaman W, Kivisakk P, Reddy J, Chitnis T, Raddassi K, Imitola J, Bradshaw E, Kuchroo VK, Yagita H, Sayegh MH, and Khoury SJ. Distinct functions of autoreactive memory and effector CD4+ T cells in experimental autoimmune encephalomyelitis. 2008. Am. J. Pathol. 173: 411-22. PMID: 18583313.
Massilamany C, Steffen D, and Reddy J. An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice. 2010. J. Neuroimmunol. 219: 17-24. PMID: 20005578.
Thulasingam S, Massilamany C, Gangaplara A, Dai H, Yarbaeva S, Subramaniam S, Riethoven JJ, Eudy J, Lou M, and Reddy J. miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells. 2011. Mol. Cell. Biochem. 352(1-2):181-8. PMID: 21350856.
Massilamany C, Gangaplara A, Gardner D, Musser J, Steffen D, Somerville G, and Reddy J. TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells. 2011. Mol. Cell. Biochem. 355(1-2):75-82. PMID: 21519920.
Massilamany C, Gangaplara A, Chapman N, Rose N, and Reddy J. Detection of cardiac myosin heavy chain-α-specific CD4 cells by using MHC class II/IA^k tetramers in A/J mice. 2011. J. Immunol. Methods. 372: 107-118. PMID: 21782819.
Massilamany C, Gangaplara A, Steffen D, and Reddy J. Identification of novel mimicry epitopes for cardiac myosin heavy chain-α that induce autoimmune myocarditis in A/J mice. 2011. Cell Immunol. 271(2):438-49. PMID: 21939961.
Massilamany C, Thulasingam S, Steffen D, and Reddy J. Gender differences in CNS autoimmunity induced by mimicry epitope for PLP 139-151 in SJL mice. 2011. J. Neuroimmunol. 230: 95-104. PMID: 20950867.
Massilamany C, Upadhyaya B, Gangaplara A, Kuszynski C, and Reddy J. Detection of autoreactive CD4 T cells using major histocompatibility complex class II dextramers. 2011. BMC Immunol. 12:40. PMID: 21767394. (highlighted as a featured and a highly accessed article).
Massilamany C, Asojo O, Gangaplara A, Steffen D, and Reddy J. Identification of a second mimicry epitope from Acanthamoeba castellanii that induce CNS autoimmunity by generating cross-reactive T cells for MBP 89-101 in SJL mice. 2011. Int. Immunol. 23 (12):729-39 (highlighted as the Editor’s Choice featured article of December issue). PMID: 22058327.
Gangaplara A, Massilamany C, Brown, DM, Delhon G, Pattnaik A, Chapman N, Rose N, Steffen D, and Reddy J. Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-alpha-reactive CD4 T cells in A/J mice. 2012. Clin. Immunol. 144: 237-249. PMID: 22854287.
Massilamany C, Gangaplara A, Kim H, Stanford C, Rathnaiah G, Steffen D, Lee J, Reddy J. Copper-zinc superoxide dismutase-deficient mice show increased susceptibility to experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein 35-55. 2013. J. Neuroimmunol. Mar 15;256 (1-2):19-27. PMID: 23294897.
Gebregiworgis T, Massilamany C, Gangaplara A, Thulasingam S, Kolli V, Werth MT, Dodds ED, Steffen D, Reddy J, Powers R. Potential of urinary metabolites for diagnosing multiple sclerosis. 2013. ACS Chem. Biol. Apr 19;8(4):684-90. PMID: 23369377.
Gangaplara A, Massilamany C, Steffen D, Reddy J. Mimicry epitope from Ehrlichia canis for interphotoreceptor retinoid-binding protein 201-216 prevents autoimmune by acting as altered peptide ligand. 2013. J. Neuroimmunol. Oct 15;263(1-2):98-107. PMID: 24029580.
Massilamany C, Gangaplara A, Jia T, Elowsky C, Kang G, Riethoven JJ, Li Q, Zhou Y, Reddy J. Direct staining with major histocompatibility complex class II dextramers permits detection of antigen-specific, autoreactive CD4 T cells in situ. 2014. PLoS One. Jan 27;9(1). PMID: 24475302.
Massilamany C, Marciano-Cabral F, Rocha-Azevedo Bd, Jamerson M, Gangaplara A, Steffen D, Zabad R, Illes Z, Sobel RA, Reddy J. SJL Mice Infected with Acanthamoeba castellanii Develop Central Nervous System Autoimmunity through the Generation of Cross-Reactive T Cells for Myelin Antigens. 2014. PLoS One. May 30;9(5). PMID: 24879066.
Massilamany C., Khalilzad V, Gangaplara A., Steffen D., Othman S.F., Reddy, J. Non-invasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse, 2014. J. Vis. Exp. Jun 20;(88). PMID: 24998332.
Massilamany C, Gangaplara A, Jia T, Elowsky C, Li Q, Zhou Y, and Reddy J. In situ detection of autoreactive CD4 1 T cells in the brain and heart using major histocompatibility complex class II dextramers. 2014. J Vis Exp. Aug 1;(90). doi: 10.3791/51679. PMID: 25145797.
Massilamany C, Gangaplara A, and Reddy J. Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy. 2014 Dec 15;177(2):330-9. PMID: 25449464
Massilamany, C†., Gangaplara, A†., Basavalingappa, R. H., Rajasekaran, R. A., Vu, H., Riethoven, J. J., Steffen, D., Pattnaik, A.K., and Reddy, J. 2015. Mutations in the 5' NTR and the Non-Structural Protein 3A of the Coxsackievirus B3 Selectively Attenuate Myocarditogenicity. PloS one 10: e0131052. (†equal contributors) (PMID: 26098885)
Massilamany, C†., Gangaplara, A†., and Reddy, J. 2015. Environmental microbes and uveitis: is microbial exposure always bad? Scandinavian journal of immunology 81: 469-475. (†equal contributors) (PMID: 25833717)
Krishnan, B., Massilamany, C., Basavalingappa, R. H., Rajasekaran, R. A., Kuszynski, C., Switzer, B., Peterson, D. A., and Reddy, J. 2015. Versatility of using major histocompatibility complex class II dextramers for derivation and characterization of antigen-specific, autoreactive T cell hybridomas. Journal of immunological methods. (PMID: 26268454)
Krishnan B, Massilamany C, Basavalingappa RH, Rajasekaran RA, Kuszynski C,Switzer B, Peterson DA, Reddy J. 2015. Versatility of using major histocompatibility complex class II dextramers for derivation and characterization of antigen-specific, autoreactive T cell hybridomas. J Immunol Methods. (PMID: 26268454)
Jia T, Anandhan A, Massilamany C, Rajasekaran RA, Franco R, Reddy J. 2015. Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation. J Neuroimmune Pharmacol. (PMID: 26416183)
Gebregiworgis T, Nielsen HH, Massilamany C, Gangaplara A, Reddy J, Illes Z, Powers R. 2016. A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica. J Proteome Res. (PMID: 26759122)
Massilamany C, Gangaplara A, Basavalingappa RH, Rajasekaran RA, Khalilzad-Sharghi V, Han Z, Othman S, Steffen D, Reddy J. 2016. Localization of CD8 T cell epitope within cardiac myosin heavy chain-α334-352 that induces autoimmune myocarditis in A/J mice. Int J Cardiol. (PMID: 26422020)
Massilamany C, Mohammed A, Loy JD, Purvis T, Krishnan B, Basavalingappa RH, Kelley CM, Guda C, Barletta RG, Moriyama EN, Smith TP, Reddy J. 2016. Whole genomic sequence analysis of Bacillus infantis: defining the genetic blueprint of strain NRRL B-14911, an emerging cardiopathogenic microbe. BMC Genomics. (PMID: 27557119)
Basavalingappa RH, Massilamany C, Krishnan B, Gangaplara A, Kang G, Khalizad V, Han Z, Othman S, Li Q, Riethoven JJ, Sobel RA, Steffen D and Reddy J. 2016. Identification of an epitope from adenine nucleotide translocator 1 that induces inflammation in heart in A/J mice. American Journal of Pathology. 186(12):3160-3175. (PMID: 27876151)
Alkheraif AA, Topliff CL, Reddy J., Massilamany C, Donis RO, Meyers G, Eskridge KM, Kelling CL. 2017. Type 2 BVDV N(pro) suppresses IFN-1 pathway signaling in bovine cells and augments BRSV replication. Virology. Jul;507:123-134. (PubMed PMID: 28432927)
Krishnan B, Massilamany C, Basavalingappa RH, Gangaplara A, Kang G, Li Q, Uzal FA, Strande JL, Delhon GA, Riethoven JJ, Steffen D, Reddy J. 2017. Branched chain α-ketoacid dehydrogenase kinase 111-130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A/J mice. Immun Inflamm Dis. Dec;5(4):421-434. (PubMed PMID: 28597552)
Basavalingappa, RH., Massilamany, C., Krishnan, B., Gangaplara, A., Afzal, ZM., Strande, JL., Steffen, D., and Reddy, J. 2017. β1-Adrenergic Receptor Contains Multiple IAk and IEk Binding Epitopes that Induce T Cell Responses with Varying Degrees of Autoimmune Myocarditis in A/J Mice. Frontiers in Immunology (in press)
Krishnan, B., Massilamany, C., Basavalingappa, RH., Gangaplara, A., Afzal, ZM., Khalilzad-Sharghi, V., Zhou, Y., Nandi, S., Mishra, PK., Sobel, RA., Strande, JL., Riethoven, JJ., Steffen, D., and Reddy, J.. 2017. Epitope Mapping of SERCA2a Identifies an Antigenic Determinant that Induces Mainly Atrial Myocarditis in A/J mice. Journal of immunology (in press)

Invited reviews

Reddy J, Massilamany C, Buskiewicz I, Huber SA. Autoimmunity in viral myocarditis. 2013. Curr Opin Rheumatol. Jul;25(4):502-8. PMID: 23656709.
Massilamany C, Huber SA, Cunningham MW, Reddy J. Relevance of molecular mimicry in the mediation of infectious myocarditis. 2014. J. Cardiovasc. Transl. Res. Mar;7(2):165-71. PMID: 24263348.
Massilamany C, Koenig A, Reddy J, Huber S, Buskiewicz I. 2016. Autoimmunity in picornavirus infections. Curr Opin Virol. (PMID: 26554915).

Invited book chapters

Massilamany, C., and Reddy, J., 2011. Autoimmunity in the Mediation of Granulomatous Amoebic Encephalitis: Implications for Therapy, p. 307-328. In S. Tkachev (ed.), Non-Flavivirus Encephalitis. InTech, Croatia.

PRESENTATIONS

Reddy J, Wilkie BN, Mallard BA, and Rosendal S. Cytokines in pigs bred selectively for high and low immune response. IV International Veterinary Immunology Symposium, 1995 July 16-21, Davis, California, USA. Vet. Immunol. Immunopathol. 54: 259 (invited paper).
Reddy J, Wilkie BN, and Mallard BA. Mitogen activation of pig blood mononuclear cells produces distinct cytokine patterns in vitro. 78^th Annual Conference of Research Workers in Animal Diseases, 1997 Nov 10-11, Chicago, USA.
Reddy J, Wilkie BN, Mallard BA, and Borgs P. Cytokines in Mycoplasma hyorhinis infection in pigs bred selectively for high and low immune response. Fifth Annual International Cytokine Society Conference, 1997 Nov 9-13, Lake Tahoe, Nevada, USA.
Reddy J, Borgs P, and Wilkie BN. Cytokine mRNA expression in leukocytes of efferent lymph from stimulated porcine lymph nodes and in cutaneous delayed-type hypersensitivity sites. 79^th Annual Conference of Research Workers in Animal Diseases, 1998 Nov 11-13, Chicago USA.
Reddy J, Bettelli E, Nicholson L, Waldner H, Wucherpfennig K,and Kuchroo V. Enumeration of Proteolipid Protein 139-151-reactive T cells using MHC II (I-A^s) tetramers in Murine Experimental Autoimmune encephalomyelitis. Experimental Biology (FASEB meeting), "Translating the Genome" April 20-24, 2002, New Orleans, Louisiana; 2^nd Annual Federation of Clinical Immunology Societies meeting, June 28-July 1, 2002, San Francisco, CA.
Kuchroo V, Illes Z, and Reddy J. Promiscuous expression of myelin antigen, proteolipid protein in the thymus affects repertoire development and susceptibility to CNS autoimmune disease, experimental autoimmune encephalomyelitis. American Society for Neurochemistry Meeting, May 3-5, 2003, Orange County, CA (oral presentation).
Reddy J, Illes Z, Zhang X, Encinas J, Pyrdol J, Nicholson L, Sobel RA, Wucherpfennig KW, and Kuchroo VK. Genetic resistance to autoimmunity is mediated by autoantigen-specific CD4⁺CD25⁺ regulatory cells Fifth annual Federation of Clinical Immunology Societies meeting, May 12-16, 2005, Boston, MA. Clinical Immunology, suppl. 1, 2005: S93, S96 and S102 (scored in top 10 % of poster submissions).
Massilamany C, Thulasingam S, Steffen D, and Reddy J. An epitope from Acanthamoeba castellanii induces clinical signs of autoimmune encephalomyelitis in SJL mice by molecular mimicry. 97th Annual meeting of The American Association of Immunologists (AAI), Baltimore, MD, May 7-11, 2010.
Massilamany C, Gangaplara A, Chapman N, Rose N, and Reddy J. Detection of cardiac myosin-specific CD4 T cells by using MHC II / IA^k tetramers in A/J mice. 97th Annual meeting of the AAI, Baltimore, MD, May 7-11, 2010.
Gangaplara A, Massilamany C, Waldner H, and Reddy J. Role of reactive oxygen species in gender-associated autoimmunity. 97th Annual meeting of the AAI, Baltimore, MD, May 7-11, 2010.
Massilamany C, Gangaplara A, Steffen D, and Reddy J. Identification of novel microbial mimics for cardiac myosin heavy chain-α 334-352 that induce autoimmune myocarditis in A/J mice. 14th International Congress of Immunology, Kobe, Japan. August 22-27, 2010.
Massilamany C, Steffen D, and Reddy J. Identification of a second mimicry epitope from Acanthamoeba castellanii that induces CNS autoimmunity through the generation of cross-reactive T cells for myelin basic protein 89-101. 98th Annual meeting the AAI, San Francisco, CA, May 13-17, 2011 (oral presentation)
Massilamany C, Gangaplara A, Gardner DJ, Steffen D, Somerville G, and Reddy J. TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells. 98th Annual meeting of the AAI, San Francisco, CA, May 13-17, 2011.
Upadhyaya BP, Massilamany C, Gangaplara A, and Reddy J. MHC Dextramers enhance the detection sensitivity of antigen-specific autoreactive CD4 cells. 98th Annual meeting of the AAI, San Francisco, CA, May 13-17, 2011.
Massilamany C, Gangaplara A, Upadhyaya BP, Jamerson M, Cabral FM, Steffen D, and Reddy J. Acanthamoeba castellanii induces the generation of proteolipid protein 139-151-reactive T cells and predispose to CNS autoimmunity in SJL mice. Federation of Clinical Immunology Societies (FOCIS) 2011, Washington DC, June 23-26, 2011.
Thulasingam S^†, Massilamany C, Gangaplara A, Yarbaeva S, Subramaniam S, Riethoven JJ, Eudy J, Lou M and Reddy J. miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells. FOCIS 2011, Washington DC, June 23-26, 2011. (scored in top 10% of poster presentations).
Gangaplara A, Massilamany C, Steffen D, and Reddy J. Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-α-reactive T cells in A/J mice. FOCIS 2011, Washington DC, June 23-26, 2011.
Massilamany C, Gangaplara A, Rathnaiah, G, Steffen D, Lee J, and Reddy J. Copper zinc superoxide dismutase 1-deficient mice show increased susceptibility to MOG 35-55-induced EAE. 99th Annual meeting of The American Association of Immunologists, Boston, MA, May 4-8, 2012. Annual Retreat of the Redox Biology Center, Nebraska City, NE, April 13 - 15, 2012 (oral presentation). Summer course: Redox Regulation, Oxidative Stress and Selenoproteins. Karolinska Institutet, Stockholm, Sweden. June 11-15, 2012.
Gangaplara A, Massilamany C, Madayiputhiya N, Nandakumar R, Kuszynski C, Steffen D, and Reddy J. Mimicry epitope from Ehrlichia canis for interphotoreceptor retinoid-binding protein ameliorates autoimmune uveoretinitis by acting as altered peptide ligand in A/J mice. 99th Annual meeting of the AAI, Boston, MA, May 4-8, 2012.
Massilamany C, Gangaplara A, Kuzynski C, Nandakumar R, Madayiputhiya N, Steffen D, and Reddy J. Gender-biased differences in the expression of proteins in proteolipid protein 139-151-specific CD4 T cells derived from autoimmune-prone, SJL mice. FOCIS 2012, Vancouver, Canada, June 20-23, 2012.
Gangaplara A, Massilamany C, Pattnaik A, Steffen D, Reddy, J. Determination of the generation and functionalities of coxsackievirus B3-specific T cells using MHC class II tetramers in the murine model of viral myocarditis. FOCIS 2012, Vancouver, Canada, June 20-23, 2012.
Massilamany C.*, Khalilzad V.*, Gangaplara A., Steffen D., Othman S.F.^¥, and Reddy J.^¥ Magnetic resonance microscopic imaging of hearts reveals structural and functional defects in autoimmune myocarditic mice. Annual meeting of Conference of Research Workers in Animal Diseases, Chicago, IL, December 2-4, 2012. (^*equal contributors; ^¥corresponding authors)
Massilamany C., Jia T., Kang G., Zhou Y., Li Q and Reddy J. In situ detection of autoreactive CD4 T cells in the mouse models of autoimmune diseases. 100th Annual meeting of The AAI, Honolulu, Hawaii, May 3-7, 2013
Massilamany C., Jamerson M., Madayiputhiya N., Nandakumar R., Cabral FM., Sejbaek TM., Illes Z and Reddy J. An evidence for a potential linkage between Acanthamoeba infections and multiple sclerosis. 100th Annual meeting of The AAI, Honolulu, Hawaii, May 3-7, 2013.
Gangaplara A., Massilamany C., Steffen D., Huber S and Reddy J. Cardiac myosin heavy chain-α 334-352 is immunogenic in C57Bl/6 mice but fails to induce autoimmune myocarditis. FOICS 2013 meeting, Boston, MA, June 27-30, 2013
Gangaplara A., Massilamany C., Steffen D., Pattnaik A., Huber S and Reddy J. An evidence for the pathogenic role for virus-specific T cells in the mouse model of coxsackievirus B3-induced myocarditis. 15^th International Congress of Immunology, Milan, Italy, August 22-27, 2013
Gebregiworgis T^†., Massilamany C^†., Gangaplara A^†., Nielssen H., Werth M., Steffen D., Zabad R., Illes Z., Powers R and Reddy J. NMR metabolomics: a diagnostic tool for Multiple Sclerosis. 15^th International Congress of Immunology, Milan, Italy, August 22-27, 2013 (^†equal contributors).
Massilamany C., Khalilzad V., Gangaplara A., Steffen D., Othman S.F., Huber, S.A. and Reddy J. Delineating autoimmunity in infectious myocarditis. The Myocarditis Foundation grant recipient workshop in conjunction with the Heart Failure Society of America’s Annual Scientific Meeting, Orlando, FL, Sept 21-22, 2013 (Invited oral presentation)
Krishnan C, Massilamany C, Smith T, Loy JD, BarlettaR, Reddy J. Bacillus infantis NRRL B-14911-induced myocarditis: a novel disease model to study the autoimmune mechanisms of myocardial injuries in the myocarditis-susceptible, A/J mice. 101^th Annual meeting of the AAI, Pittsburg, PA, May 2-6, 2014.
MassilamanyC, Steffen D, Reddy J. Delineating the role of cardiac myosin-specific CD8 T cells in autoimmune myocarditis. 101^th Annual meeting of the AAI, Pittsburg, PA, May 2-6, 2014.
Gangaplara A, Massilamany C, Steffen D, Reddy J. Gender differences in the development of autoimmune myocarditis induced with cardiac myosin heavy chain-alpha, 334-352 in C57Bl/6 mice. 101th Annual meeting of the AAI, Pittsburg, PA, May 2-6, 2014.
Jia T, Massilamany C, and Reddy J. Delineating the mechanisms of immunomodulatory effects of sex steroids in autoreactive T cells. 101th Annual meeting of the AAI, Pittsburg, PA, May 2-6, 2014.
Krishnan B,MassilamanyC, PetersonD, Reddy J. Quick and efficient method of deriving antigen-specific, T cell hybridomas and their phenotypic characterization using major histocompatibility complex class II dextramers. Annual meeting of the FOCIS, Chicago, IL, June 25-28, 2014.
Helle H. Nielsen, Lars P. Kristensen, Hans C. Beck, Reddy J, Illes Z. The proteome profile of the urine is different in patients with neuromyelitis optica compared to multiple sclerosis and healthy subjects. ACTRIMS-ECTRIMS (joint meeting), September 10-13, 2014.
Massilamany C, Krishnan B, Rajsekaran AR, Gangaplara A, Elowsky C, Zhou Y, Kuszynski C, and Reddy J. Versatility of Major Histocompatibility Complex Class II Dextramers for Detection, and Functional Characterization of Antigen-Specific, Autoreactive CD4 T Cells in the Mouse Models of Autoimmune Diseases. Cytokines Down Under: From Bench to Beyond, Annual meeting of the International Cytokine and Interferon Society, 26 - 29 October 2014, Melbourne, Australia. 2014
Massilamany C, Krishnan B, Smith TP, Moriyama E, Barletta, RG, Loy JD and Reddy J. Role of Bacillus infantis NRRL B-14911 in the mediation of autoimmune myocarditis. Cytokines Down Under: From Bench to Beyond, Annual meeting of the International Cytokine and Interferon Society, 26 - 29 October 2014, Melbourne, Australia. 2014.
Basavalingappa RH, Massilamany C, Rajasekaran RA, Steffen, D, and Reddy J. Identification of immunogenic epitopes of β-adrenergic receptor 1 that induce heart autoimmunity in A/J mice. 102nd Annual meeting of The American Association of Immunologists, New Orleans, LA, May 8-12, 2015.
Massilamany C, Rajasekaran RA, Basavalingappa RH, Steffen D, and Reddy, J. Viral Myocarditis Induced with Coxsackievirus B3 Involves the Mediation of Mono Antigen-Specific Autoreactive CD4 and CD8 T Cell Responses. Federation of Clinical Immunology Societies 2015 meeting, San Diego, CA, June 24-27, 2015.
Jia T, Anandan A, Massilamany C, Rajasekaran RA, Cruz R-F, and Reddy J. Evidence for autophagy as a possible mechanism that contributes to the antiproliferative effects of testosterone in the autoreactive T cells. Federation of Clinical Immunology Societies 2015 meeting, San Diego, CA, June 24-27, 2015.
Gebregiworgis, T., Massilamany C, Gangaplara A, Steffen D, Nielsen H, Illes Z, and Reddy J, and R. Powers. Urine metabolomics: a potential approach to diagnose and monitor Multiple Sclerosis. 56th Experimental Nuclear Magnetic Resonance Conference, Pacific Grove, CA, United States, Apr 18-24, 2015.
Massilamany, C., Mohammed, A., Loy, J. D. , Purvis, T., Krishnan, B., Basavalingappa, R.H., Kelly, C., Guda, C., Barletta, R. G., Moriyama, E., Smith, T., and Reddy, J. Whole genomic sequence analysis of Bacillus infantis: defining the genetic blueprint of strain NRRL B-14911, an emerging cardiopathogenic microbe. BMC Genomics. International Conference on Intelligent Biology and Medicine, Indianapolis, IN, November 13-15, 2015 (invited oral presentation).
Basavalingappa RH, Massilamany C, Rajasekaran R, Steffen D and Reddy J Identification of immunogenic epitopes of β-adrenergic receptor 1 that induce heart autoimmunity in A/J mice. 102nd Annual meeting of American Association of Immunologists, New Orleans, Louisiana, May 8-12, 2015.
Massilamany, C., Gangaplara, A., Basavalingappa, R., Rajasekaran, R., Steffen, D., Pattnaik, A., Reddy, J. 103rd Annual meeting of The American Association of Immunologist, Seattle, WA, "Mutation in the 5'NTR and non-structural protein 3A of the coxsackievirus B3 selectively attenuate myocarditogenicity", May 13, 2016.
Basavalingappa, R., Massilamany, C., Krishnan, B., Gangaplara, A., Kang, G., Khalizar, V., Han, Z., Othman, S., Li, Q., Riethoven, J., Sobel, R., Steffen, D., Reddy, J. 97th conference of Research Workers in Animal Diseases Meeting & Seventh U.S BVDV Symphosium, Chicago IL, "Identification of an Epitope from Adenine Nucleotide Translocator 1 That Induces Inflammation in Heart in A/J Mice", December 6, 2016.
Krishnan, B., Massilamany, C., Basavalingappa, R., Gangaplara, A., Kang, G., Li, Q., Uzal, F., Strande, J., Delhon, G., Riethoven, J., Steffen, D., Reddy, J. 97th conference of Research Workers in Animal Diseases Meeting & Seventh U.S BVDV Symphosium, Chicago Il, "Identification of branched chain alpha-ketoacid dehydrogenase kinase as a target autoantigen in the induction of cardiac autoimmunity through the generation of autoreactive T cell A/J mice", December 6, 2016.
Basavalingappa R, Gangaplara A, Massilamany C, Krishnan B, Jia T, Steffen D and Reddy J Federation of Clinical Immunology Societies. Chicago. Coxsackievirus B3 viral protein1 possesses multiple immunodominant epitopes that induce differential antigen-specific, CD4 and CD8 T cell responses in A/J mice. June 14-17, 2017.