SUPPRESSOR T CELL CIRCUITS-猫眼课题宝

抑制 T 细胞电路

DOI：

10.1111/j.1749-6632.1982.tb36115.x

发表时间：

1982

期刊：

Annals of the New York Academy of Sciences

影响因子：

5.2

通讯作者：

中科院分区：

综合性期刊3区

文献类型：

作者：

B. Benacerraf;M. Greene;M. Sy;M. Dorf

在过去的几年中，一些实验室对抗原特异性T细胞的特异性抑制进行了深入研究。这揭示了免疫反应被T细胞负调控的方式中存在着意想不到的复杂性。突出的发现是：(1)特异性抑制现象涉及几组具有明确性质和特征表面标记的T细胞的相互作用。这些T细胞各自产生特定的因子，这些因子可以被证明介导它们的精确调节功能(3)它们的特异性要么是抗原的特异性，要么是决定它们相互作用某些方面的免疫球蛋白的特异性。(4)这些电路中的某些抑制性T细胞（Ts）具有由小鼠H-2复合体的I-J亚区编码的决定因子，这似乎也限制了通路中某些关键步骤的相互作用，类似于I-A和I-E亚区对辅助T细胞（Th）相互作用的限制。(5)因此，回路中的抑制性T细胞相互作用可以被证明是由VII基因和主要组织相容性复合体（MHC）基因在适当的步骤下控制的。主要基于我们实验室获得的结果，我们已经研究了抑制T细胞对几种模型的调节，我们最近提出，所有小鼠系统中的T细胞抑制都是通过一个共同的主要途径进行的，该途径涉及三种具有不同特性的T细胞亚群的顺序相互作用，我们将其命名为T、T、T和T。我们还提出，这一整体方案可用于整合在其他实验室开发的系统中获得的数据。我们现在建议回顾一下我们用来区分和识别通路中不同细胞的标准。我们还将介绍我们实验室对T细胞抑制回路、它们的细胞和它们的特定产物的分析的最新数据。然后，我们将讨论在将复杂数据整合到一个可推广的方案中所遇到和现在面临的问题，以确定在多大程度上需要假设某些系统特有的变量。最后，我们将尝试解决一些主要的尚未解决的基本问题，例如在分子水平上观察到的I-J限制的意义以及辅佐细胞在T细胞抑制途径中抗原呈递的可能作用。表1描述了用于分析所调查系统的标准。考虑的主要区别点是：(1)相关细胞或因子的结合特异性，特别是其受体是独特型（抗原特异性）还是抗独特型，(2)因子产生者和受体细胞的膜表型和药物敏感性，(3)遗传限制（H-2或V）的参与

Over the last few years, several laboratories have intensively studied specific suppression by antigen-specific T cells. This has revealed the existence of unsuspected complexity in the manner in which the immune response is negatively regulated by T cells. The salient findings are that (1 ) The specific suppression phenomena involve the interactions of several sets of T cells with defined properties and characteristic surface markers.' (2) These T cells each produce specific factors that can be shown to mediate their precise regulatory function.2 ( 3 ) Their specificity is either for the antigen or for the immunoglobulin idiotypes that determine certain aspects of their interactions. (4) Certain of the suppressor T cells (Ts) in these circuits bear determinants coded for by the I-J subregion of the murine H-2 complex, which also appears to restrict the interactions at certain critical steps in the pathway, in a way similar to the restrictions imposed by the I-A and I-E subregions on helper T cell (Th) interactions.' (5) Accordingly, suppressor T cell interactions in the circuit can be shown to be governed by both VII genes and major histocompatibility complex (MHC) genes at appropriate steps. Based primarily on the results obtained in our laboratories, where the regulation of several models by suppressor T cells has been investigated, we have recently proposed that T cell suppression in all murine systems proceeds by a common major pathway involving the sequential interactions of three T cell subsets with distinct properties, which we have termed Ts,, Ts,, and Ts,.' We have also proposed that this overall scheme may be used to integrate the data obtained in systems developed in other laboratories. We now propose to review the criteria that we have used to distinguish and identify the distinct cells in the pathway. We shall also describe the latest data from our laboratories on the analysis of T cell suppressor circuits, their cells, and their specific products. We shall then discuss the problems we have encountered and are now facing in integrating the complex data in a generalizable scheme to determine to what extent one needs to postulate variants unique to certain systems. Finally, we shall try to address some of the major unresolved fundamental issues, such as the significance of the observed I-J restrictions at the molecular level and the possible role of antigen presentation by acccssory cells in the T cell suppressor pathway. TABLE 1 describes the criteria used to analyze the systems under investigation. The major distinguishing points considered were: ( 1 ) the binding specificity of the relevant cell or factor and, in particular, whether its receptor is idiotypic (antigen specific) or anti-idiotypic, (2) the membrane phenotype and drug sensitivity of the factor producer and the acceptor cell, ( 3 ) the involvement of genetic restrictions (H-2 or V,) in

Suppressor factor from a T cell hybrid inhibits delayed-type hypersensitivity responses to azobenzenearsonate.