T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node
T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node
复制标题
DOI：
10.1073/pnas.0306407101
复制
发表时间：
2004-01-27
影响因子：
11.1
通讯作者：
Parker, I
中科院分区：
文献类型：
--
作者：
Miller, MJ;Hejazi, AS;Parker, I
树突状细胞(DC)在外周组织中摄取抗原，并迁移到淋巴结，在那里它们将MHC II类结合的抗原呈递给CD4(+)T细胞。我们使用双光子显微镜，在没有相关抗原的情况下，对完整淋巴结内DC和T细胞之间相互作用的单细胞动力学进行成像。通过皮下注射含羧基荧光素二乙酸酯琥珀酰亚胺酯(CFSE)的明胶佐剂对DC进行体内荧光标记。24~72 h引流淋巴结内可见CD11c(+)、CD11b(+)和CD8(+)阳性树突状细胞。标记的DC在B细胞滤泡附近的T细胞区缓慢蜿蜒(2-3um·min(-1))，但强烈地伸展出长而灵活的树突。当T细胞沿着随机路径自主移动时，T细胞和DC之间的接触就会发生。此外，T细胞没有聚集在DC周围，它们接近和离开DC的相对速度是相等的，这意味着T细胞不是被趋化梯度吸引到DC，而是偶然地遇到它们。T细胞/DC接触主要发生在距离DC胞体一臂远的树突上，通常持续约3分钟，使单个DC每小时可与多达5,000个T细胞相互作用。我们的结论是，动态DC手势和随机T细胞运动共同增强了对T细胞库的随机扫描，从而能够快速启动免疫反应。
Dendritic cells (DCs) ingest antigens in peripheral tissues and migrate to lymph nodes where they present MHC class II-bound antigen to CD4(+) T cells. We used two-photon microscopy to image the single-cell dynamics of interactions between DCs and T cells within intact lymph nodes in the absence of relevant antigen. DCs were fluorescently labeled in vivo by cutaneous injection of alum adjuvant including carboxyfluorescein diacetate succinimidyl ester (CFSE). CFSE-positive DCs (CD11c(+), CD11b(+), and low-to-intermediate CD8(+)) were observed in draining lymph nodes 24-72 h later. Labeled DCs meandered slowly (2-3 mum(.)min(-1)) in the T cell zone near B cell follicles but vigorously extended long agile dendrites. Encounters between T cells and DCs arose as T cells moved autonomously along random paths. Moreover, T cells did not accumulate around DCs, and their relative velocities approaching and departing DCs were equivalent, implying that T cells are not attracted toward DCs by chemotactic gradients but rather encounter them by chance. T cell/DC contacts occurred primarily on dendrites at arm's length from the DC soma and typically lasted approximate to3 min, enabling an individual DC to interact with up to 5,000 T cells per hour. We conclude that dynamic DC gesticulation and random T cell motility together enhance the stochastic scanning of the T cell repertoire, thereby enabling rapid initiation of the immune response.