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

par Chang, Ying;De Nadai, Patricia ;Azzaoui, Imane;Morales, Olivier;Delhem, Nadira;Vorng, Han;Tomavo, Stanislas;Ait Yahia, Saliha;Zhang, Guizhen;Wallaert, Benoît;Chenivesse, Cécile;Tsicopoulos, Anne
Référence The FASEB journal, 24, 12, page (5063-5072)
Publication Publié, 2010-12

Article révisé par les pairs

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Résumé :

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-β1 but not IL-4, IFN-γ, 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.