Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1High germinal center-associated subpopulation
Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1High germinal center-associated subpopulation
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DOI：
10.4049/jimmunol.179.8.5099
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发表时间：
2007-10-15
影响因子：
4.4
通讯作者：
Cyster, Jason G.
中科院分区：
文献类型：
--
作者：
Haynes, Nicole M.;Allen, Christopher D. C.;Cyster, Jason G.
TH细胞进入初级B细胞滤泡的途径依赖于CXCR5。然而，CXCR5对T细胞的诱导是否足以确定它们的卵泡位置尚不清楚。在这项研究中，我们发现，除非消除CCR7配体的平衡影响，否则转基因CXCR5的过度表达不足以促进幼稚T细胞进入卵泡。相反，在没有CXCR5的情况下，抗原结合的T细胞在B/T交界处的定位可能发生。当T细胞缺乏CXCR5时，生发中心(GC)的反应降低了2倍，尽管这些T细胞能够访问生发中心。最后，发现CXCR5(高)CCR7(低)T细胞IL-4转录和程序性细胞死亡基因-1(PD-1)表达增加，而PD-1(高)细胞在缺乏T细胞CXCR5或在GC形成中受损的小鼠中减少。总体而言，这些发现进一步了解了CXCR5和CCR7表达的变化如何调节抗体应答过程中Th细胞的定位，并表明PD-1(高)滤泡性Th细胞亚群的发展和/或维持依赖于与GC B细胞的适当相互作用。
Th cell access to primary B cell follicles is dependent on CXCR5. However, whether CXCR5 induction on T cells is sufficient in determining their follicular positioning has been unclear. In this study, we find that transgenic CXCR5 overexpression is not sufficient to promote follicular entry of naive T cells unless the counterbalancing influence of CCR7 ligands is removed. In contrast, the positioning of Ag-engaged T cells at the B/T boundary could occur in the absence of CXCR5. The germinal center (GC) response was 2-fold reduced when T cells lacked CXCR5, although these T cells were able to access the GC. Finally, CXCR5(high) CCR7(low) T cells were found to have elevated IL-4 transcript and programmed cell death gene-1 (PD-1) expression, and PD-1(high) cells were reduced in the absence of T cell CXCR5 or in mice compromised in GC formation. Overall, these findings provide further understanding of how the changes in CXCR5 and CCR7 expression regulate Th cell positioning during Ab responses, and they suggest that development and/or maintenance of a PD-1(high) follicular Th cell subset is dependent on appropriate interaction with GC B cells.