In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines.
In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines.
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DOI：
10.1084/jem.190.8.1123
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发表时间：
1999-10-18
影响因子：
15.3
通讯作者：
Cyster, J G
中科院分区：
文献类型：
--
作者：
Ansel, K M;McHeyzer-Williams, L J;Ngo, V N;McHeyzer-Williams, M G;Cyster, J G
抗原激活的 CD4 T 细胞迁移到淋巴组织的 B 细胞区域对于建立 T 细胞依赖性抗体反应非常重要。在这里，我们发现，当动物在促进 T 细胞迁移到滤泡的条件下进行免疫时，CXC 趋化因子受体 (CXCR)5（B 淋巴细胞趋化剂 (BLC) 的受体）在体内抗原特异性 CD4 T 细胞上表达上调。 BLC 的次级卵泡原位杂交显示，在地幔区高表达，在生发中心低表达。当直接离体测试时，CXCR5hi T 细胞对 BLC 表现出强烈的趋化反应。与此同时，CXCR5hi 细胞对 T 区趋化因子、EB 病毒诱导的分子 1 (EBI-1) 配体趋化因子 (ELC) 和次级淋巴组织趋化因子 (SLC) 的反应性降低。过继转移后，CXCR5hi CD4 T 细胞没有迁移到滤泡，这表明免疫后可能会发生额外的变化，有助于将 T 细胞引导到滤泡。为了进一步探讨 T 细胞是否可以获得迁移到滤泡的内在能力，研究了来自 MRL-lpr 小鼠的 CD4−CD8− 双阴性 (DN) T 细胞。这些 T 细胞通常积聚在 MRL-lpr 小鼠的卵泡内。转移至野生型受体后，DN T 细胞迁移至所有次级淋巴组织的滤泡近端区域。总而言之，我们的研究结果表明，对组成型表达的淋巴组织趋化因子的反应性重编程在 T 细胞迁移到淋巴组织 B 细胞区室中发挥着重要作用。
Migration of antigen-activated CD4 T cells to B cell areas of lymphoid tissues is important for mounting T cell–dependent antibody responses. Here we show that CXC chemokine receptor (CXCR)5, the receptor for B lymphocyte chemoattractant (BLC), is upregulated on antigen-specific CD4 T cells in vivo when animals are immunized under conditions that promote T cell migration to follicles. In situ hybridization of secondary follicles for BLC showed high expression in mantle zones and low expression in germinal centers. When tested directly ex vivo, CXCR5hi T cells exhibited a vigorous chemotactic response to BLC. At the same time, the CXCR5hi cells showed reduced responsiveness to the T zone chemokines, Epstein-Barr virus–induced molecule 1 (EBI-1) ligand chemokine (ELC) and secondary lymphoid tissue chemokine (SLC). After adoptive transfer, CXCR5hi CD4 T cells did not migrate to follicles, indicating that additional changes may occur after immunization that help direct T cells to follicles. To further explore whether T cells could acquire an intrinsic ability to migrate to follicles, CD4−CD8− double negative (DN) T cells from MRL-lpr mice were studied. These T cells normally accumulate within follicles of MRL-lpr mice. Upon transfer to wild-type recipients, DN T cells migrated to follicle proximal regions in all secondary lymphoid tissues. Taken together, our findings indicate that reprogramming of responsiveness to constitutively expressed lymphoid tissue chemokines plays an important role in T cell migration to the B cell compartment of lymphoid tissues.