TY - JOUR
T1 - Cutting edge
T2 - Induction of B7-H4 on APCs through IL-10: Novel suppressive mode for regulatory T cells
AU - Kryczek, Ilona
AU - Wei, Shuang
AU - Zou, Linhua
AU - Zhu, Gefeng
AU - Mottram, Peter
AU - Xu, Huanbin
AU - Chen, Lieping
AU - Zou, Weiping
PY - 2006/7/1
Y1 - 2006/7/1
N2 - Multiple modes of suppressive mechanisms including IL-10 are thought to be implicated in CD4+ CD25+ regulatory T (Treg) cell-mediated suppression. However, the cellular source, role, and molecular mechanism of IL-10 in Treg cell biology remain controversial. We now studied the interaction between Treg cells and APCs. We demonstrate that Treg cells, but not conventional T cells, trigger high levels of IL-10 production by APCs, stimulate APC B7-H4 expression, and render APCs immunosuppressive. Initial blockade of B7-H4 reduces the suppressive activity mediated by Treg cell-conditioned APCs. Further, APC-derived, rather than Treg cell-derived, IL-10 is responsible for APC B7-H4 induction. Therefore, Treg cells convey suppressive activity to APCs by stimulating B7-H4 expression through IL-10. Altogether, our data provide a novel cellular and molecular mechanism for Treg cell-mediated immunosuppression at the level of APCs, and suggest a plausible mechanism for the suppressive effect of IL-10 in Treg cell-mediated suppression.
AB - Multiple modes of suppressive mechanisms including IL-10 are thought to be implicated in CD4+ CD25+ regulatory T (Treg) cell-mediated suppression. However, the cellular source, role, and molecular mechanism of IL-10 in Treg cell biology remain controversial. We now studied the interaction between Treg cells and APCs. We demonstrate that Treg cells, but not conventional T cells, trigger high levels of IL-10 production by APCs, stimulate APC B7-H4 expression, and render APCs immunosuppressive. Initial blockade of B7-H4 reduces the suppressive activity mediated by Treg cell-conditioned APCs. Further, APC-derived, rather than Treg cell-derived, IL-10 is responsible for APC B7-H4 induction. Therefore, Treg cells convey suppressive activity to APCs by stimulating B7-H4 expression through IL-10. Altogether, our data provide a novel cellular and molecular mechanism for Treg cell-mediated immunosuppression at the level of APCs, and suggest a plausible mechanism for the suppressive effect of IL-10 in Treg cell-mediated suppression.
UR - http://www.scopus.com/inward/record.url?scp=33745317769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745317769&partnerID=8YFLogxK
M3 - Article
C2 - 16785496
AN - SCOPUS:33745317769
SN - 0022-1767
VL - 177
SP - 40
EP - 44
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -