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Kryczek I, Wei S, Zou L et al.Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells. J Immunol 177:40-44

Department of Surgery, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
The Journal of Immunology (Impact Factor: 5.36). 08/2006; 177(1):40-4. DOI: 10.4049/jimmunol.177.1.40
Source: PubMed

ABSTRACT 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.

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Available from: Huanbin Xu, Aug 13, 2015
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    • "Recently, T reg cells have also been shown to trigger high levels of IL-10 production by APCs and in turn stimulate B7-H4 expression in an autocrine fashion and render these APCs immunosuppressive (Kryczek et al., 2006). "
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    • "This data indicates that the CD11b + IL-10-producing cells in the ascites are comprised of a myeloid population distinct from granulocytes , with phenotypic markers of monocytes, macrophages, and dendritic cells. T regulatory cells (T reg ), another suppressive population known to produce IL-10 in cancer (Liyanage et al., 2002; Marshall et al., 2004; Kawaida et al., 2005; Kryczek et al., 2006a; Mougiakakos et al., 2010), were comparatively assessed with the use of MAFIA/FOXP3-GFP mice in which both the CD115 + and FOXP3 + cells express GFP. MDSCs were identified as CD115-GFP + CD11b + cells, and T reg were identified as CD45 + CD4 + FOXP3-GFP + cells within the ascites. "
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