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- Multiple sclerosis (3)
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Articles 1 - 9 of 9
Full-Text Articles in Medical Microbiology
Coxsackievirus B3 Infection Leads To The Generation Of Cardiac Myosin Heavy Chain-Α-Reactive Cd4 T Cells In A/J Mice, Arunakumar Gangaplara, Chandirasegaran Massilamany, Deborah M. Brown, Gustavo A. Delhon, Asit K. Pattnaik, Nora Chapman, Noel Rose, David J. Steffen, Jay Reddy
Coxsackievirus B3 Infection Leads To The Generation Of Cardiac Myosin Heavy Chain-Α-Reactive Cd4 T Cells In A/J Mice, Arunakumar Gangaplara, Chandirasegaran Massilamany, Deborah M. Brown, Gustavo A. Delhon, Asit K. Pattnaik, Nora Chapman, Noel Rose, David J. Steffen, Jay Reddy
Jay Reddy Publications
Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an underlying mechanism, but direct evidence of its role is lacking. To delineate autoimmune response in CVB3 myocarditis, we used IAk dextramers for cardiac myosin heavy chain (Myhc)-α 334–352. We have demonstrated that myocarditis-susceptible A/J mice infected with CVB3 generate Myhc-α-reactive CD4 T cells and such a repertoire was absent in naïve mice as measured by proliferative response to Myhc-α 334–352 and IAk dextramer staining. We also detected Myhc-α 334–352 dextramer+ cells in the hearts of CVB3-infected mice. The autoreactive …
Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy
Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy
Jay Reddy Publications
We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139–151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89–101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108–120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89–101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108–120 develop encephalomyelitis similar to the disease induced by the cognate peptide. …
Distinct Functions Of Autoreactive Memory And Effector Cd4+ T Cells In Experimental Autoimmune Encephalomyelitis, Wassim Elyaman, Pia Kivisäkk, Jay Reddy, Tanuja Chitnis, Khadir Raddassi, Jaime Imitola, Elizabeth Bradshaw, Vijay K. Kuchroo, Hideo Yagita, Mohamed H. Sayegh, Samia J. Khoury
Distinct Functions Of Autoreactive Memory And Effector Cd4+ T Cells In Experimental Autoimmune Encephalomyelitis, Wassim Elyaman, Pia Kivisäkk, Jay Reddy, Tanuja Chitnis, Khadir Raddassi, Jaime Imitola, Elizabeth Bradshaw, Vijay K. Kuchroo, Hideo Yagita, Mohamed H. Sayegh, Samia J. Khoury
Jay Reddy Publications
The persistence of human autoimmune diseases is thought to be mediated predominantly by memory T cells. We investigated the phenotype and migration of memory versus effector T cells in vivo in experimental autoimmune encephalomyelitis (EAE). We found that memory CD4+ T cells up-regulated the activation marker CD44 as well as CXCR3 and ICOS, proliferated more and produced more interferon-γ and less interleukin-17 compared to effector T cells. Moreover, adoptive transfer of memory T cells into T cell receptor (TCR)αβ-/- recipients induced more severe disease than did effector CD4+ T cells with marked central nervous system inflammation and …
Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo
Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo
Jay Reddy Publications
Myelin proteolipid protein (PLP) 139–151 is an immunodominant peptide that induces experimental autoimmune encephalomyelitis (EAE) in H-2s SJL/J mice. While PLP 139–151-specific TCR transgenic (tg) 4E3 mice develop fulminant spontaneous disease on the susceptible SJL/J background, spontaneous EAE is dramatically reduced on the H-2s congenic B10.S background. On this resistant background, we observed a high frequency of positively selected tg CD42CD82 (DN) thymocytes and peripheral DN tg T cells. Splenic DN tg T cells responded to anti-CD3 stimulation similarly to CD41 cells, but proliferative and cytokine responses to PLP 139–151 were blunted, implying that CD4 coreceptor down-regulation modulated …
Monoclonal Antibodies To Distinct Regions Of Human Myelin Proteolipid Protein Simultaneously Recognize Central Nervous System Myelin And Neurons Of Many Vertebrate Species, Edward A. Greenfield, Jay Reddy, Andrew Lees, Charissa A. Dyer, Omanand Koul, Khuong Nguyen, Shannon Bell, Nasim Kassam, Julian Hinojoza, Mary Jane Eaton, Marjorie B. Lees, Vijay K. Kuchroo, Raymond A. Sobel
Monoclonal Antibodies To Distinct Regions Of Human Myelin Proteolipid Protein Simultaneously Recognize Central Nervous System Myelin And Neurons Of Many Vertebrate Species, Edward A. Greenfield, Jay Reddy, Andrew Lees, Charissa A. Dyer, Omanand Koul, Khuong Nguyen, Shannon Bell, Nasim Kassam, Julian Hinojoza, Mary Jane Eaton, Marjorie B. Lees, Vijay K. Kuchroo, Raymond A. Sobel
Jay Reddy Publications
Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a member of the proteolipid gene family (pgf). It is an evolutionarily conserved polytopic integral membrane protein and a potential autoantigen in multiple sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ, monoclonal antibodies (mAbs) specific for different regions of human PLP (50–69, 100–123, 139–151, 178–191, 200–219, 264–276) were generated and used to immunostain CNS tissues of representative vertebrates. mAbs to each region recognized whole human PLP on Western blots; the anti-100–123 mAb did not recognize DM-20, the PLP isoform that lacks residues 116–150. All of …
Or.76. Myelin Specific Regulatory T-Cells Expand From Naturally Occurring Regulatory T-Cells And Accumulate In The Cns During Eae [Abstract Only], Thomas Korn, Jay Reddy, Wenda Gao, Terry Strom, Mohamed Oukka, Vijay K. Kuchroo
Or.76. Myelin Specific Regulatory T-Cells Expand From Naturally Occurring Regulatory T-Cells And Accumulate In The Cns During Eae [Abstract Only], Thomas Korn, Jay Reddy, Wenda Gao, Terry Strom, Mohamed Oukka, Vijay K. Kuchroo
Jay Reddy Publications
FoxP3 is a lineage specific marker for regulatory T-cells (Treg). We have generated FoxP3 knock-in (KI) mice by introducing a bicistronic GFP reporter into the endogenous FoxP3 locus, allowing us to faithfully track T-reg in vivo. Recently, we have also generated a MOG 35-55/IAb-tetramer. The combination of these two technologies enables us to study the in vivo behavior of myelin specific T-reg and effector T-cells (T-eff) during EAE. Upon immunization with MOG 35-55, we identified a population of MOG-tetramerreactive T-reg in the peripheral lymphoid compartment. T-reg trafficked to the CNS where they were readily detected as early as day 10 …
Or.107. Tim-1 Plays A Crucial Role In The Expansion Of Autopathogneic T-Cells And Regulation Of Autoimmunity [Abstract Only], Sheng Xioa, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Ana Anderson, Zheng Zhang, Cristina Gutierrez, Raymond Sobel, Dale Umetsu, Hideo Yagita, Hisaya Akiba, Mohamed Sayegh, Rosemarie Dekruyff, Vijay K. Kuchroo
Or.107. Tim-1 Plays A Crucial Role In The Expansion Of Autopathogneic T-Cells And Regulation Of Autoimmunity [Abstract Only], Sheng Xioa, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Ana Anderson, Zheng Zhang, Cristina Gutierrez, Raymond Sobel, Dale Umetsu, Hideo Yagita, Hisaya Akiba, Mohamed Sayegh, Rosemarie Dekruyff, Vijay K. Kuchroo
Jay Reddy Publications
T-cell immunoglobulin and mucin (TIM) family Members are differentially expressed on Th1 and Th2 cells. Polymorphisms of TIM-1 have been associated with susceptibility to asthma; however, its role in regulating autoimmunity has not been studied. Here, we have used an agonistic antiTIM-1 antibody (Ab, Clone 3B3) which has previously been shown to costimulate T-cell activation and expansion, to analyze the role of TIM-1 in the development and regulation of experimental autoimmune encephalomyelitis (EAE). Treatment with 3B3 dramatically enhances the severity of EAE as well as the frequency of encephalitogenic CD4+ T-cells and the production of IFN-g and IL-17 by these …
Peptide 15-Mers Of Defined Sequence That Substitute For Random Amino Acid Copolymers In Amelioration Of Experimental Autoimmune Encephalomyelitis, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Masha Fridkis-Hareli, Vijay K. Kuchroo, Jack L. Strominger
Peptide 15-Mers Of Defined Sequence That Substitute For Random Amino Acid Copolymers In Amelioration Of Experimental Autoimmune Encephalomyelitis, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Masha Fridkis-Hareli, Vijay K. Kuchroo, Jack L. Strominger
Jay Reddy Publications
Myelin basic protein (MBP) is a major candidate autoantigen in multiple sclerosis (MS). Its immunodominant epitope, MBP 85–99, forms a complex with human leukocyte antigen (HLA)-DR2 with which multiple sclerosis is genetically associated. Copolymer 1 (Copaxone), a random amino acid copolymer [poly (Y,E,A,K)n] as well as two modified synthetic copolymers [poly (F,Y,A,K)n and poly (V,W,A,K)n] also form complexes with HLA-DR2 (DRA DRB1*1501) and compete with MBP 85–99 for binding. Moreover, two high-affinity synthetic peptide 15-mers that could inhibit binding even more effectively were previously designed. Here, we show that further-modified peptide 15-mers inhibited even more strongly (in order J5 > J3 …
Myelin Proteolipid Protein-Specific Cd4+ Cd25+ Regulatory Cells Mediate Genetic Resistance To Experimental Autoimmune Encephalomyelitis, Jay Reddy, Zsolt Illés, Xingmin Zhang, Jeffrey Encinas, Jason Pyrdol, Lindsay Nicholson, Raymond A. Sobel, Kai W. Wucherpfennig, Vijay K. Kuchroo, James P. Allison
Myelin Proteolipid Protein-Specific Cd4+ Cd25+ Regulatory Cells Mediate Genetic Resistance To Experimental Autoimmune Encephalomyelitis, Jay Reddy, Zsolt Illés, Xingmin Zhang, Jeffrey Encinas, Jason Pyrdol, Lindsay Nicholson, Raymond A. Sobel, Kai W. Wucherpfennig, Vijay K. Kuchroo, James P. Allison
Jay Reddy Publications
SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139–151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139–151-specific T cells in the naive repertoire of SJL mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139–151-reactive T cells in both strains by using IAs/PLP 139–151 tetramers. SJL and B10.S mice had similar frequencies of tetramer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the …