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Monocyte‐derived dendritic cells promote T f ollicular h elper cell differentiation

Abstract : To be effective, protein priming must induce the development of a distinct lineage of CD4(+) T cells named T follicular helper (Tfh) cells, which regulate the differentiation of high-affinity memory B cells and long-lived plasma cells. In this context, we tested how adjuvantation with CpG, the Toll-like receptor 9 agonist used in clinics, contributes to antigen-specific T-cell-dependent B-cell responses in vivo. We found that addition of CpG to other vaccine adjuvant increased the differentiation of antigen-specific Tfh cells without changing the overall magnitude of the T-cell response. This phenomenon correlated with an enhancement of the germinal centre reaction, antigen-specific plasma cells and circulating antibodies. We comprehensively demonstrated that, in addition to the classical Tfh-cell differentiation mediated by conventional DC, the promoting effect due to CpG was orchestrated in vivo by antigen presentation and IL-6 secreted by monocyte-derived dendritic cells (DC) as shown in their absence. Thus, while conventional DC initiate T-cell responses, targeting monocyte-derived DC specifically enhances the Tfh programme needed to regulate high-affinity B-cell protection in vivo.
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Submitted on : Tuesday, January 14, 2020 - 6:30:48 PM
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Svetoslav Chakarov, Nicolas Fazilleau. Monocyte‐derived dendritic cells promote T f ollicular h elper cell differentiation. EMBO Molecular Medicine, Wiley Open Access, 2014, 6 (5), pp.590-603. ⟨10.1002/emmm.201403841⟩. ⟨inserm-02439894⟩

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