Follicular dendritic cell regulation of CXCR4-Mediated germinal center CD4 T cell migration
Follicular dendritic cell regulation of CXCR4-Mediated germinal center CD4 T cell migration
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DOI：
10.4049/jimmunol.173.10.6169
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发表时间：
2004-11-15
影响因子：
4.4
通讯作者：
Burton, GF
中科院分区：
文献类型：
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作者：
Estes, JD;Thacker, TC;Burton, GF
滤泡树突状细胞（FDC）上调CD 4 T细胞上的趋化因子受体CXCR 4，并且在体内与FDC相邻的生发中心（GC）T细胞（CD 4（+）CD 57（+））的主要亚群表达高水平的CXCR 4。因此，我们推断GC T细胞会主动迁移到基质细胞衍生因子-1（CXCL 12）（CXCR 4配体），并使用Transwell迁移试验对GC T细胞和其他表达低得多的CXCR 4水平的CD 4 T细胞（CD 57（-））进行了测试。出乎意料的是，GC T细胞几乎对CXCL 12无反应，而CD 57（-）CD 4 T细胞尽管CXCR 4表达降低，但仍有效迁移。相反，GC T细胞有效地迁移到B细胞趋化因子-1/CXCL 13和FDC上清液，其含有由FDC产生的CXCL 13。重要的是，GC T细胞对CXCL 12的无反应性与G蛋白信号传导调节因子（RGS）、RGS 13和RGS 16、mRNA的离体高表达以及体内蛋白质的表达相关。此外，FDC上调非GC T细胞中RGS 13和RGS 16 mRNA的表达，导致其向CXCL 12的迁移受损。最后，GC T细胞在不存在FDC的情况下下调RGS 13和RGS.16的表达，并重新获得向CXCL 12的迁移能力。尽管GC T细胞表达高水平的CXCR 4，但通过该受体的信号传导似乎被FDC介导的RGS 13和RGS 16表达特异性抑制。因此，FDC似乎直接影响淋巴滤泡内的GC T细胞迁移。
Follicular dendritic cells (FDCs) up-regulate the chemokine receptor CXCR4 on CD4 T cells, and a major subpopulation of germinal center (GC) T cells (CD4(+)CD57(+)), which are adjacent to FDCs in vivo, expresses high levels of CXCR4. We therefore reasoned that GC T cells would actively migrate to stromal cell-derived factor-1 (CXCL12), the CXCR4 ligand, and tested this using Transwell migration assays with GC T cells and other CD4 T cells (CD57(-)) that expressed much lower levels of CXCR4. Unexpectedly, GC T cells were virtually nonresponsive to CXCL12, whereas CD57(-)CD4 T cells migrated efficiently despite reduced CXCR4 expression. In contrast, GC T cells efficiently migrated to B cell chemoattractant-l/CXCL13 and FDC supernatant, which contained CXCL13 produced by FDCs. Importantly, GC T cell nonresponsiveness to CXCL12 correlated with high ex vivo expression of regulator of G protein signaling (RGS), RGS13 and RGS16, mRNA and expression of protein in vivo. Furthermore, FDCs up-regulated both RGS13 and RGS16 mRNA expression in non-GC T cells, resulting in their impaired migration to CXCL12. Finally, GC T cells down-regulated RGS13 and RGS.16 expression in the absence of FDCs and regained migratory competence to CXCL12. Although GC T cells express high levels of CXCR4, signaling through this receptor appears to be specifically inhibited by FDC-mediated expression of RGS13 and RGS16. Thus, FDCs appear to directly affect GC T cell migration within lymphoid follicles.