MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们已经质疑了长期以来关于生理学的教条， 淋巴结的T细胞依赖区的结构，并进化出一种 通过结合免疫组织学、体内 示踪剂研究和细胞培养。首先，在T细胞依赖区， T细胞在高度组织化的迷宫中迁移。 它的拓扑结构 迷宫是最佳的有效细胞接触：a）狭窄的水性 通道内衬B）富含细胞外基质的基质细胞 适合于为细胞迁移提供牵引力，和c）通过 抗原呈递指状突树突状细胞（IDC） 用于呈递抗原。 第二，有效 网状内皮细胞屏障，其将该隔室与 淋巴/鼻窦第三，淋巴液中可溶性示踪剂的移动 通过沿着淋巴细胞转运进入T细胞依赖性区域， 由基质细胞包裹的前所未有的管道系统 形成迷宫的墙壁。 第四，基质细胞似乎 调节淋巴结的环境， 可溶性因子如TGF β和趋化因子如IL-8和MCP-1。 了解这些特征对于治疗那些 免疫反应是缺乏的（如癌症）或夸大的（如 如关节炎和糖尿病）。 此外，在最初的体外研究中，我们 发现淋巴结基质细胞显著促进T细胞感染 HIV病毒。 我们正在研究 淋巴细胞迁移的过程，特别强调 丝状伪足 我们正在系统地分析人类和小鼠的外周血 子集来理解表面分子的整体， 每个.总的来说，在生物学领域需要更好的战略。 社区来组织有关人类蛋白质的大量信息;我们是 开发一种国际资源，我们将其命名为PROW [蛋白质 网上的评论]来帮助解决这个问题。

We have questioned longstanding dogmas regarding the physiology and architecture of T-cell dependent area of lymph nodes, and evolved a much richer understanding by a combination of immunohistology, in vivo tracer studies, and cell culture. First, in the T-cell-dependent area T cells migrate in a highly organized labyrinth. The topology of that labyrinth is optimized for efficient cell contact: a) narrow aqueous channels lined b) by stromal cells rich in extracellular matrix suitable for providing traction for cell migration and c) by antigen-presenting interdigitating dendritic cells (IDC) specialized for presenting antigen. Second, there is an effective reticulo-endothelial cell barrier which isolates this compartment from the lymph/sinuses. Third, the movement of soluble tracers from lymph into the T cell dependent areas occurs by transport along an unprecedented conduit system ensheathed by the very stromal cells that form the walls of the labyrinth. Fourth, the stromal cells appear to condition the environment of the lymph node by producing their own soluble factors such as TGFb, and chemokines such as IL-8 and MCP-1. Understanding these features is important to treating diseases where immune responses are deficient (such as cancers) or exaggerated (such as arthritis and diabetes). Moreover, in initial in vitro studies, we find that lymph node stromal cells markedly facilitate T cell infection by HIV virus. We are investigating the morphological and biochemical processes whereby lymphocytes migrate, with particular emphasis on filopodia. We are systematically characterizing human and mouse peripheral blood subsets to understand the ensemble of surfaces molecules expressed by each. In general, better strategies will be required in the biological community to organize the mass of information on human proteins; we are developing an international resource which we designate PROW [Protein Reviews on the Web] to help address this problem.