T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible.
CD4(+) T cells constitutively expressing the immune-tolerogenic HLA-G have been described recently as a new type of nT(reg) (HLA-G(pos) T(reg)) in humans. HLA-G(pos) T(reg) accumulate at sites of inflammation and are potent suppressors of T cell proliferation in vitro, suggesting their role in immune regulation. We here characterize the mechanism of how CD4(+) HLA-G(pos) T(reg) influence autologous HLA-G(neg) T(resp) function. Using a suppression system free of APC, we demonstrate a T-T cell interaction, resulting in suppression of HLA-G(neg) T(resp), which is facilitated by TCR engagement on HLA-G(pos) T(reg). Suppression is independent of cell-cell contact and is reversible, as the removal of HLA-G(pos) T(reg) from the established coculture restored the proliferative capability of responder cells. Further, HLA-G(pos) T(reg)-mediated suppression critically depends on the secretion of IL-10 but not TGF-beta.
Huang
Yu-Hwa
YH
Department of Neurology, University of Wuerzburg, Wuerzburg, Germany.
Zozulya
Alla L
AL
Weidenfeller
Christian
C
Schwab
Nicholas
N
Wiendl
Heinz
H
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10