TY - JOUR
T1 - Immunoregulation of encephalitogenic MBP-NAc1-11-reactive T cells by CD4+ TCR-specific T cells involves IL-4, IL-10 and IFN-γ
AU - Adlard, Kirsten
AU - Tsaknaridis, Laura
AU - Beam, Aaron
AU - Bebo, Bruce F.
AU - Vandenbark, Arthur A.
AU - Offner, Halina
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - The generation of TCR transgenic (Tg) mice expressing a BV8S2 (Vβ8 subfamily 2) chain specific for the encephalitogenic NAc1-11 region of MBP provides a unique system for evaluating the mechanisms involved in anti-TCR immunoregulation of EAE. In a previous study, we showed that vaccination with BV8S2 protein induced specific T cells that inhibited proliferation responses and encephalitogenic activity of MBP-reactive T cells in vitro, and resulted in a skewed production of Th2 cytokines by the MBP-reactive T cells. These data suggested that regulation of the encephalitogenic T cells was mediated by inhibitory cytokines rather than through a deletional mechanism. In the current study, we have employed the BV8S2 Tg mouse model to address the issue of which cytokines produced by anti-TCR-reactive T cells can regulate the function of encephalitogenic Th1 cells. Utilizing neutralizing anti-cytokine antibodies to reverse inhibitory effects of supernatants from BV8S2-specific T cells, we found that IL-4, IL-10, and to a lesser extent, IFN-γ and TGF-β, were the major regulatory cytokines responsible for inhibiting encephalitogenic activity, proliferation, and IFN-γ secretion of MBP-NAc1-11-reactive Th1 cells. These results indicate that cytokine regulation is the major mechanism through which TCR specific CD4+ T cells regulate encephalitogenic and potentially other bystander Th1 cells.
AB - The generation of TCR transgenic (Tg) mice expressing a BV8S2 (Vβ8 subfamily 2) chain specific for the encephalitogenic NAc1-11 region of MBP provides a unique system for evaluating the mechanisms involved in anti-TCR immunoregulation of EAE. In a previous study, we showed that vaccination with BV8S2 protein induced specific T cells that inhibited proliferation responses and encephalitogenic activity of MBP-reactive T cells in vitro, and resulted in a skewed production of Th2 cytokines by the MBP-reactive T cells. These data suggested that regulation of the encephalitogenic T cells was mediated by inhibitory cytokines rather than through a deletional mechanism. In the current study, we have employed the BV8S2 Tg mouse model to address the issue of which cytokines produced by anti-TCR-reactive T cells can regulate the function of encephalitogenic Th1 cells. Utilizing neutralizing anti-cytokine antibodies to reverse inhibitory effects of supernatants from BV8S2-specific T cells, we found that IL-4, IL-10, and to a lesser extent, IFN-γ and TGF-β, were the major regulatory cytokines responsible for inhibiting encephalitogenic activity, proliferation, and IFN-γ secretion of MBP-NAc1-11-reactive Th1 cells. These results indicate that cytokine regulation is the major mechanism through which TCR specific CD4+ T cells regulate encephalitogenic and potentially other bystander Th1 cells.
KW - Experimental autoimmune encephalomyelitis
KW - Regulatory cytokines
KW - TCR regulation
KW - Transgenic mice
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U2 - 10.3109/08916939908994069
DO - 10.3109/08916939908994069
M3 - Article
C2 - 10789989
AN - SCOPUS:0033491623
SN - 0891-6934
VL - 31
SP - 237
EP - 248
JO - Autoimmunity
JF - Autoimmunity
IS - 4
ER -