Cutting Edge: Induction of B7-H4 on APCs through IL-10: Novel Suppressive Mode for Regulatory T Cells

• Published in: The Journal of immunology (1950) 2006-07, Vol.177 (1), p.40-44
• Main Authors: Kryczek, Ilona, Wei, Shuang, Zou, Linhua, Zhu, Gefeng, Mottram, Peter, Xu, Huanbin, Chen, Lieping, Zou, Weiping
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Blocking - pharmacology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; B7-1 Antigen - biosynthesis; B7-1 Antigen - genetics; B7-1 Antigen - immunology; B7-1 Antigen - physiology; Cells, Cultured; Coculture Techniques; Down-Regulation - genetics; Down-Regulation - immunology; Female; Humans; Interleukin-10 - biosynthesis; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Up-Regulation - genetics; Up-Regulation - immunology; V-Set Domain-Containing T-Cell Activation Inhibitor 1
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.177.1.40

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.