The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo
The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo
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DOI：
10.4049/jimmunol.175.4.2340
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发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Okumura, K
中科院分区：
文献类型：
--
作者：
Akiba, H;Takeda, K;Okumura, K
ICOS是表达于活化T细胞上的共刺激分子CD 28家族的新成员。其配体B7 RP-1在B细胞上组成型表达。虽然ICOS/B7 RP-1相互作用的阻断抑制了T细胞依赖性Ab的产生和生发中心的形成，但其机制仍不清楚。我们检测了ICOS/B7 RP-1对体内CXCR 5（+）滤泡B辅助性T（T-FH）细胞产生的贡献，所述细胞优先迁移到B细胞区，在那里它们为B细胞提供同源帮助。在脾脏中，抗B7 RP-1 mAb处理的或ICOS缺陷的小鼠表现出对SRBC初次或二次免疫应答的CXCR 5（+）T-FH细胞和花生凝集素（+）生发中心B细胞的发育显著受损。CD 4（+）T细胞CXCR 5表达与ICOS表达相关。连续转移实验表明，CXCR 5（+）T-FH细胞的发育通过与B细胞的相互作用而增强，这被抗B7 RP-1 mAb处理所消除。淋巴结中CXCR 5（+）T-FH细胞的发育也受到抗B7 RP-1 mAb处理的抑制。这些结果表明ICOS/B7 RP-1相互作用在体内CXCR 5（+）T-FH细胞的发育中起着重要作用。
ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell-dependent Ab production and germinal center formation, the mechanism remains unclear. We examined the contribution of ICOS/B7RP-1 to the generation of CXCR5(+) follicular B helper T (T-FH) cells in vivo, which preferentially migrate to the B cell zone where they provide cognate help to B cells. In the spleen, anti-B7RP-1 mAb-treated or ICOS-deficient mice showed substantially impaired development of CXCR5(+) T-FH cells and peanut agglutinin(+) germinal center B cells in response to primary or secondary immunization with SRBC. Expression of CXCR5 on CD4(+) T cells was associated with ICOS expression. Adoptive transfer experiments showed that the development of CXCR5(+) T-FH cells was enhanced by interaction with B cells, which was abrogated by anti-B7RP-1 mAb treatment. The development of CXCR5(+) T-FH cells in the lymph nodes was also inhibited by the anti-B7RP-1 mAb treatment. These results indicated that the ICOS/B7RP-1 interaction plays an essential role in the development of CXCR5(+) T-FH cells in vivo.