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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

Johns Hopkins University, Baltimore, Maryland, United States
The Journal of Immunology (Impact Factor: 4.92). 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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    • "Interleukin 10 (IL-10) and transforming growth factor b (TGFb ) are anti-inflammatory and immunosuppressive cytokines that can contribute to the immune escape of neoplastic cells (Kryczek et al., 2006; Matsuda et al., 1994; Thomas & Massague, 2005). IL- 10 prevents antigen presentation by macrophages and dendritic cells, reducing the expression of the MHC class I molecules on the cell surface (Matsuda et al., 1994), regulating the differentiation of T regulatory (T reg) cells (Kryczek et al., 2006) and inducing the formation of a tumour cell phenotype resistant to the action of cytotoxic T lymphocytes (CTLs) (Kurte et al., 2004). TGF-b contributes to the loss of differentiation of tumour cells (Ma et al., 2013), angiogenesis (Pertovaara et al., 1994) and the synthesis of proteolytic enzymes (Kim, Shang, Chen, Pflugfelder, & Li, 2004). "
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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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