Heterogeneity of Phenotype and Function Reflects the Multistage Development of T Follicular Helper Cells.

Heterogeneity of Phenotype and Function Reflects the Multistage Development of T Follicular Helper Cells.
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DOI:
10.3389/fimmu.2017.00489
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发表时间:
2017
影响因子:
7.3
通讯作者:
Gray D
Gray D
中科院分区:
医学2区
文献类型:
--
作者:
Trüb M;Barr TA;Morrison VL;Brown S;Caserta S;Rixon J;Ivens A;Gray D

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T滤泡辅助细胞(TFH)为生发中心(GC)的形成提供重要信号,但TFH群体具有异质性。虽然PD1hi Tfh在GC反应中很重要,但PD1lo Tfh样亚集的功能尚不清楚。我们表明,这些细胞,像PD1hi GC-Tfh一样,依赖于B细胞;然而,它们进入卵泡的过程独立于CXCR5或与B细胞的同源相互作用。向PD1hi Tfh的分化依赖于MHC II类与B细胞的相互作用,需要CXCR5。我们的数据表明,Tfh的分化途径最初是B细胞独立的,然后依赖于非同源的B细胞相互作用,最后与B细胞和CXCR5-配体的同源相互作用允许GC-Tfh的形成。PD1lo-Tfh样细胞产生早期的细胞因子反应,可能是CD4记忆细胞的前体。
T follicular helper cells (Tfh) provide crucial signals for germinal center (GC) formation, but Tfh populations are heterogeneous. While PD1hi Tfh are important in the GC response, the function of the PD1lo Tfh-like subset is unknown. We show that these cells, like the PD1hi GC–Tfh, depend upon B cells; however, their entry to follicles is independent of CXCR5 or cognate interactions with B cells. The differentiation into PD1hi Tfh is dependent on MHC class II interactions with B cells and requires CXCR5. Our data suggest a Tfh differentiation pathway that is initially B cell-independent, then dependent on non-cognate B cell interactions, and finally following cognate interaction with B cells and CXCR5-ligands allows the formation of GC–Tfh. The PD1lo Tfh-like cells make early cytokine responses and may represent precursors of CD4 memory cells.