Abstracts (complete list) - Wissenschaft Online

Yu-Hwa Huang, Eva Tolosa, Heinz Wiendl
Suppressive action of HLA-G-expressing T cells, a novel
population of natural regulatory cells, is independent of
antigen-presenting cell, facilitated by TCR-engagement,
involves HLA-G-ILT-2 ligation and IL-10
Regulatory T cells suppress harmful immune responses against foreign and self-antigens
and play a key role in the mechanisms of autoimmunity. We recently identified a novel
regulatory T cell population characterized by the expression of the immune-tolerogenic
molecule HLA-G (Feger et al., 2007, Blood). “HLA-G T-regulatory cells” (HLA-G Tregs)
exist in small, but sizeable quantities in peripheral blood under physiological conditions
(0.1 to 4% of T cells). Our initial phenotypcial and functional characterization revealed
that HLA-G Tregs are hypoproliferative, negative for FOXP3 and suppress autologous T
cells in a non-contact-dependent manner.
We here provide further data clarifying the mechanisms of suppression between HLA-G
Tregs and CD4 T effector cells. CD4 HLA-G Tregs suppress proliferation of autologous
polyclonal effector cells in the absence of antigen-presenting cells (APC), suggesting
non-antigenic specifically suppression. This was demonstrated in an APC-free
suppression system utilizing anti-CD3/28-beads as the stimulus for responder cells.
Suppression was depending on the effector-responder ratio but independent from cellcell
contact. Using a transwell system we could demonstrate that (i) TCR engagement
facilitates CD4 HLA-G pos Treg - mediated suppression through the production of
soluble HLA-G; (ii) Neutralization the engagement of HLA-G-ILT2 significantly reversed
suppression; (iii) CD4 HLA-Gpos Treg produced IL-10 upon TCR stimulation; (iv)
Blockage of the IL-10 receptor partially reversed suppression. In conclusion, CD4 HLA-G
pos Treg exert suppression via a non-cell-cell contact dependent mechanism that
involves HLA-G-ILT2 interaction as well as IL-10.