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Antigen‐specific TGF‐beta‐induced regulatory T cells modulate mouse splenic dendritic cell function
Author(s) -
Lu Tangying Lily,
Kim Yong Chan,
Andersson John,
Shevach Ethan M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.848.20
Subject(s) - cd86 , downregulation and upregulation , foxp3 , il 2 receptor , microbiology and biotechnology , gsk 3 , biology , antigen presenting cell , chemistry , t cell , cancer research , immunology , signal transduction , immune system , gene , biochemistry
It is widely accepted that CD4 + CD25 + Foxp3 + regulatory T cells (Treg) can suppress the activation of CD4 + CD25 − T cells. Although Treg might exert their suppressive effects directly on responder T cells, recent studies have raised the possibility that they may act on dendritic cells (DC). To examine the modulatory effect of Treg on DC, antigen‐specific Foxp3 + Treg were generated in vitro by stimulation of Foxp3 − T cells in the presence of TGF‐β. Peptide‐pulsed DC were then cultured alone, with Treg alone, with naïve T cells (Tn) of the same specificity, or with Treg and Tn. DC cultured in the absence of T cells spontaneously matured in culture as demonstrated by upregulation of CD86 expression. CD86 upregulation was enhanced 3‐fold by culture with Tn and slightly inhibited by co‐culture with Treg alone. The Tn‐induced upregulation of CD86 was completely inhibited by co‐culture with Treg. DC co‐cultured with Tn and Treg also failed to induce the proliferation of Tn both in vitro and in vivo . The inhibitory effects of Treg on DC maturation could be reversed by the addition of SB216763, a glycogen synthase kinase‐3 (GSK3) inhibitor, but not by anti‐IL‐10, ‐TGF‐β, or ‐CTLA4. These studies demonstrate that the immunosuppressive effects of Treg may be mediated via suppression of DC maturation/function and may involve modulation of the GSK‐3/β‐catenin pathway. Supported by NIH/NIAID.