Gerner Michael Y, Casey Kerry A, Kastenmuller Wolfgang, Germain Ronald N
Department of Immunology, University of Washington, Seattle, WA
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, LLC, Gaithersburg, MD.
J Exp Med. 2017 Oct 2;214(10):3105-3122. doi: 10.1084/jem.20170335. Epub 2017 Aug 28.
Dendritic cell (DC) subsets with biased capacity for CD4 and CD8 T cell activation are asymmetrically distributed in lymph nodes (LNs), but how this affects adaptive responses has not been extensively studied. Here we used quantitative imaging to examine the relationships among antigen dispersal, DC positioning, and T cell activation after protein immunization. Antigens rapidly drained into LNs and formed gradients extending from the lymphatic sinuses, with reduced abundance in the deep LN paracortex. Differential localization of DCs specialized for major histocompatibility complex I (MHC I) and MHC II presentation resulted in preferential activation of CD8 and CD4 T cells within distinct LN regions. Because MHC I-specialized DCs are positioned in regions with limited antigen delivery, modest reductions in antigen dose led to a substantially greater decline in CD8 compared with CD4 T cell activation, expansion, and clonal diversity. Thus, the collective action of antigen dispersal and DC positioning regulates the extent and quality of T cell immunity, with important implications for vaccine design.
具有偏向性激活CD4和CD8 T细胞能力的树突状细胞（DC）亚群在淋巴结（LN）中呈不对称分布，但这如何影响适应性反应尚未得到广泛研究。在此，我们使用定量成像技术来研究蛋白质免疫后抗原扩散、DC定位和T细胞激活之间的关系。抗原迅速引流至LN并形成从淋巴窦延伸的梯度，在深层LN副皮质中丰度降低。专门负责主要组织相容性复合体I（MHC I）和MHC II呈递的DC的差异定位导致在不同的LN区域内优先激活CD8和CD4 T细胞。由于专门负责MHC I的DC位于抗原递送有限的区域，与CD4 T细胞激活、扩增和克隆多样性相比，抗原剂量的适度降低导致CD8 T细胞激活的下降幅度更大。因此，抗原扩散和DC定位的共同作用调节了T细胞免疫的程度和质量，这对疫苗设计具有重要意义。
