RECEPTOR-DIRECTED FOCUSING OF LYMPHOKINE RELEASE BY HELPER T-CELLS

RECEPTOR-DIRECTED FOCUSING OF LYMPHOKINE RELEASE BY HELPER T-CELLS
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DOI:
10.1038/332378a0
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发表时间:
1988-03-24
期刊:
影响因子:
64.8
通讯作者:
JANEWAY, CA
JANEWAY, CA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
POO, WJ;CONRAD, L;JANEWAY, CA

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辅助性T细胞和B细胞之间的相互作用,导致胸腺依赖抗原抗体的产生,是免疫系统1-3中明确定义的第一个细胞相互作用;它仍然是一个范例,也是有争议的。这种相互作用的两个要求,即辅助细胞(TH)和B细胞必须识别物理上相连的抗原决定簇4,5,以及B细胞必须共享编码主要组织相容性复合体(MHC)II类分子6的基因,导致了TH-B相互作用需要两种细胞类型的密切物理联系的概念。但体外研究表明,TH可以被可溶性的、非抗原特异性的因子取代,能够激活任何B细胞分泌抗体7,8。我们先前提出,TH-B接触的要求可能是因为TH细胞以极性的方式向发生T细胞受体9-16交联的细胞膜部分释放淋巴因子。利用克隆的辅助T细胞系的人工单层,我们证明在TH细胞有限激活的条件下,淋巴因子优先于受体交联区。因此,TH-B细胞相互作用的特异性的一个重要方面是受体导向的辅助淋巴因子的极地释放。
The interaction between helper T cells and B cells, leading to the production of antibody to thymus-dependent antigens, was the first cell interaction clearly defined in the immune system1–3; it remains both paradigmatic and controversial. Two requirements of this interaction, that the helper cell (TH) and the B cell must recognize antigenic determinants that are physically linked4,5, and that the THand the B cell must share genes encoding major histocompati-bility complex (MHC) class II molecules6, led to the concept that TH–B interaction required an intimate physical association of the two cell types. Butin vitrostudies have shown that THcan be replaced by soluble, antigen-nonspecific factors, capable of activating any B cell to secrete antibody7,8. We have previously proposed that the requirements for TH–B contact might result from THcells releasing their lymphokines in a polar fashion directed at that portion of the cell membrane where T-cell receptor cross-linking is actually occurring9–16. Using an artificial monolayer of a cloned helper T-cell line, we show that lymphokines are r eleased preferentially over the area of receptor cross-linking under conditions of limited TH-cell activation. Thus, it appears that one important aspect of the specificity of TH–B cell interactions is the receptor-directed polar release of helper lymphokines.