Published online before print April 28, 2009
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Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Wuerzburg, Wuerzburg, Germany
1. Correspondence: Department of Neurology, University of Wuerzburg, Josef-Schneider-Strasse 11, 97080 Wuerzburg, Germany. E-mail: heinz.wiendl{at}klinik.uni-wuerzburg.de
ABSTRACT
CD4+ T cells constitutively expressing the immune-tolerogenic HLA-G have been described recently as a new type of nTreg (HLA-Gpos Treg) in humans. HLA-Gpos Treg 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-Gpos Treg influence autologous HLA-Gneg Tresp function. Using a suppression system free of APC, we demonstrate a T–T cell interaction, resulting in suppression of HLA-Gneg Tresp, which is facilitated by TCR engagement on HLA-Gpos Treg. Suppression is independent of cell–cell contact and is reversible, as the removal of HLA-Gpos Treg from the established coculture restored the proliferative capability of responder cells. Further, HLA-Gpos Treg-mediated suppression critically depends on the secretion of IL-10 but not TGF-β.
Key Words: tolerance suppression nonclassical MHC class-Ib molecule