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Role of IFNγ in Allograft Tolerance Mediated by CD4 + CD25 + Regulatory T Cells by Induction of IDO in Endothelial Cells
Author(s) -
Thebault P.,
Condamine T.,
Heslan M.,
Hill M.,
Bernard I.,
Saoudi A.,
Josien R.,
Anegon I.,
Cuturi M. C.,
Chiffoleau E.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2007.01960.x
Subject(s) - il 2 receptor , foxp3 , microbiology and biotechnology , immune privilege , immunology , antigen presenting cell , immune system , immune tolerance , adoptive cell transfer , interleukin 21 , biology , cancer research , medicine , t cell
Regulatory T cells have been described to specifically accumulate at the site of regulation together with effector T cells and antigen‐presenting cells, establishing a state of local immune privilege. However the mechanisms of this interplay remain to be defined. We previously demonstrated, in a fully MHC mismatched rat cardiac allograft combination, that a short‐term treatment with a deoxyspergualine analogue, LF15‐0195, induces long‐term allograft tolerance with a specific expansion of regulatory CD4 + CD25 + T cells that accumulate within the graft. In this study, we show that following transfer of regulatory CD4 + T cells to a secondary irradiated recipient, regulatory CD25 + Foxp3 + and CD25 + Foxp3 − CD4 + T cells accumulate at the graft site and induce graft endothelial cell expression of Indoleamine 2, 3‐dioxygenase (IDO) by an IFNγ‐dependent mechanism. Moreover, in vivo transfer of tolerance can be abrogated by blocking IFNγ or IDO, and anti‐IFNγ reduces the survival/expansion of alloantigen‐induced regulatory Foxp3 + CD4 + T cells. Together, our results demonstrate interrelated mechanisms between regulatory CD4 + CD25 + T cells and the graft endothelial cells in this local immune privilege, and a key role for IFNγ and IDO in this process.