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Induction of human CD4 + regulatory T cells by mycophenolic acid‐treated dendritic cells
Author(s) -
Lagaraine Christine,
Lemoine Roxane,
Baron Christophe,
Nivet Hubert,
VelgeRoussel Florence,
Lebranchu Yvon
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1007716
Subject(s) - biology , il 2 receptor , microbiology and biotechnology , in vitro , cd40 , antigen presenting cell , secretion , immunology , immune tolerance , t cell , antigen , immune system , cytotoxic t cell , biochemistry
Depending on their degree of maturation, costimulatory molecule expression, and cytokine secretion, dendritic cells (DC) can induce immunity or tolerance. DC treated with mycophenolic acid during their maturation (MPA‐DC) have a regulatory phenotype and may therefore provide a new approach to induce allograft tolerance. Purified CD4 + T cells stimulated in a human in vitro model of mixed culture by allogeneic MPA‐DC displayed much weaker proliferation than T cells activated by mature DC and were anergic. This hyporesponsiveness was alloantigen‐specific. Interestingly, T cells stimulated by MPA‐DC during long‐term coculture in four 7‐day cycles displayed potent, suppressive activity, as revealed by marked inhibition of the proliferation of naive and preactivated control T cells. These regulatory T cells (Tregs) appeared to have antigen specificity and were contact‐dependent. Tregs induced by MPA‐DC were CD25 + glucocorticoid‐induced TNFR + CTLA‐4 + CD95 + , secreted IL‐5 and large amounts of IL‐10 and TGF‐β, and displayed enhanced forkhead box p3 expression. These results obtained in vitro demonstrate that human MPA‐DC can induce allospecific Tregs that may be exploited in cell therapy to induce allograft tolerance.