The Chemoattractant Receptor Ebi2 Drives Intranodal Naive CD4+ T Cell Peripheralization to Promote Effective Adaptive Immunity
The Chemoattractant Receptor Ebi2 Drives Intranodal Naive CD4+ T Cell Peripheralization to Promote Effective Adaptive Immunity
复制标题
DOI：
10.1016/j.immuni.2019.04.001
复制
发表时间：
2019-05-21
期刊：
影响因子：
32.4
通讯作者：
Germain, Ronald N.
中科院分区：
文献类型：
--
作者：
Baptista, Antonio P.;Gola, Anita;Germain, Ronald N.
淋巴结 (LN) 将参与这种反应的抗原、抗原呈递细胞和抗原反应淋巴细胞集中在一处，从而在适应性免疫中发挥着关键作用。最近的研究揭示了这些器官内先天性和适应性免疫细胞的非随机定位，这表明显微解剖定位优化了涉及稀疏合作细胞的反应。在这里，我们报道专门负责MHC-II抗原呈递的LN cDC2树突状细胞的外周定位与趋化受体Ebi2引导的CD4(+) T细胞类似的偏皮质分布相匹配。在Ebi2缺失的情况下，CD4+T细胞会失去其定位偏向性，并在抗原识别、增殖扩张、分化、直接效应活性以及为CD8+T细胞介导的记忆反应提供帮助方面被延迟，从而限制宿主防御和疫苗反应。这些发现证明了 LN 内促进细胞反应的不同生态位的进化选择，强调了细粒度组织组织和宿主防御之间的关键联系。
Lymph nodes (LNs) play critical roles in adaptive immunity by concentrating in one location the antigens, antigen-presenting cells, and antigen-responsive lymphocytes involved in such responses. Recent studies have revealed nonrandom localization of innate and adaptive immune cells within these organs, suggesting that microanatomical positioning optimizes responses involving sparse cooperating cells. Here, we report that the peripheral localization of LN cDC2 dendritic cells specialized for MHC-II antigen presentation is matched by a similarly biased paracortical distribution of CD4(+) T cells directed by the chemoattractant receptor Ebi2. In the absence of Ebi2, CD4(+) T cells lose their location bias and are delayed in antigen recognition, proliferative expansion, differentiation, direct effector activity, and provision of help for CD8(+) T cell-mediated memory responses, limiting host defense and vaccine responses. These findings demonstrate evolutionary selection for distinct niches within the LN that promote cellular responses, emphasizing the critical link between fine-grained tissue organization and host defense.