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The chemokine CCL18 generates adaptive regulatory T cells from memory CD4 + T cells of healthy but not allergic subjects

Year: 2010

Type: article

Abstract: ABSTRACT The purpose of this study was to assess the direct effect of CCL18’ a chemokine elevated in allergic diseases and induced by Th2 cytokines’ on the polarization of human CD4 + T cells. Purified human T cells from healthy subjects were pretreated or not with CCL18’ and evaluated for cytokine production. CCL18‐pretreated memory but not naive CD4 + T cells exhibited an increased production of IL‐10 (12.3±2.6 vs. 5.6±0.9 ng/ml for medium) and TGF‐β 1 but not IL‐4’ IFN‐Y’ and IL‐17 compared with control cells. Pretreatment of highly purified CD4 + CD25” memory T cells with CCL18 led to their conversion to CD4 + CD25 + Foxp3 + regulatory T cells able to inhibit the proliferation of CD4 + CD25 – effector T cells by both cytokine and cell contact‐dependent mechanisms. However’ this regulatory effect of CCL18 was lost when T cells originated from allergic subjects in relation with a decreased binding of CCL18 to these cells [0.7±0.3 mean fluorescence intensity (MFI)] as compared to those from healthy subjects (6.0±1.7 MFI). This study is the first to define a chemokine that generates adaptive regulatory T cells from CD4 + CD25 – memory T cells. This mechanism appears defective in allergic patients and may underlie the decreased tolerance observed in allergic diseases.—Chang’ Y.’ de Nadai’ P.’ Azza‐oui’ I.’ Morales’ O.’ Delhem’ N.’ Vorng’ H.’ Tomavo’ S.’ Ait Yahia’ S.’ Zhang’ G.’ Wallaert’ B.’ Chenivesse’ C.’ Tsicopou‐los’ A. The chemokine CCL18 generates adaptive regulatory T cells from memory CD4 + T cells of healthy but not allergic subjects. FASEBJ. 24’ 5063–5072 (2010). www.fasebj.org

Source: The FASEB Journal

DOI: 10.1096/fj.10.162560