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Regulatory T cells play a role in T‐cell receptor CDR2 peptide regulation of experimental autoimmune encephalomyelitis
Author(s) -
Buenafe Abigail C.,
Andrew Shayne,
Offner Halina,
Vandenbark Arthur A.
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03531.x
Subject(s) - experimental autoimmune encephalomyelitis , t cell receptor , foxp3 , biology , immunology , t cell , population , microbiology and biotechnology , regulatory t cell , il 2 receptor , inflammation , immune system , medicine , environmental health
Summary Eliciting T‐cell receptor (TCR) ‐specific responsiveness has been known to provide an effective autoregulatory mechanism for limiting inflammation mediated by T effector cells. Our previous use of TCR peptides derived from the CDR3 regions of a pathogenic TCR effectively reversed ongoing experimental autoimmune encephalomyelitis (EAE) in a humanized TCR transgenic model. In this study, we use the TCR BV8S2 CDR2 peptide in the non‐transgenic C57BL/6 EAE model to down‐regulate the heterogeneous TCR BV8S2 + MOG‐35‐55‐specific pathogenic T‐cell population and demonstrate successful treatment of EAE after disease onset. Suppression of disease was associated with reduced MOG‐35‐55‐specific and non‐specific T‐cell production of interleukin‐17a and interferon‐γ in the central nervous system, as well as reduced numbers of CD4 + and Foxp3 + T cells in the central nervous system. With the use of Foxp3‐GFP and Foxp3 conditional knockout mice, we demonstrate that the TCR CDR2 peptide treatment effect is dependent on the presence of Foxp3 + regulatory T cells and that regulatory T cell numbers are significantly expanded in the periphery of treated mice. Hence, TCR CDR2 peptide therapy is effective in regulating heterogeneous, pathogenic T‐cell populations through the activity of the Foxp3 + regulatory T cell population.