Premium
Mechanisms of tolerance induced by TGFβ‐treated APC: CD4 regulatory T cells prevent the induction of the immune response possibly through a mechanism involving TGFβ
Author(s) -
Alard Pascale,
Clark Sherry L.,
Kosiewicz Michele M.
Publication year - 2004
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200324547
Subject(s) - biology , cd8 , transforming growth factor , cytotoxic t cell , immune tolerance , immune system , immunology , antigen , regulatory t cell , t cell , il 2 receptor , microbiology and biotechnology , in vitro , biochemistry
Abstract Transforming growth factor β (TGFβ)‐treated antigen‐presenting cells (APC) pulsed with antigen induce tolerance in mice, i.e. inhibition of IFN‐γ production and delayed type hypersensitivity response. Although evidence suggests that regulatory T cells are involved, their mechanism of action is currently unknown and is the subject of the present study. Both CD4 and CD8 splenic T cells from mice injected i.v. with adherent thioglycolate‐elicited peritoneal exudate cells cultured with TGFβ 2 and antigen (TGFβ‐treated APC) transferred tolerance to naive recipients. Interestingly, TGFβ‐treated APC from class II knockout mice were unable to induce tolerance in wild‐type mice, whereas wild‐type TGFβ‐treated APC could induce tolerance in CD8 knockout mice. TGFβ was detected in cultures of lymphoid cells from mice injected with TGFβ‐treated APC, and treatment with anti‐TGFβ antibody in vivo impaired tolerance induction. TGFβ appeared to be involved in both the development of CD4 regulatory T cells and the effector function of the CD4 regulatory T cells. In summary, the important findings in this study are that CD4, and not CD8, regulatory T cells are required for tolerance induced by TGFβ‐treated APC in naive mice, and tolerance appears to be mediated by a mechanism involving TGFβ.