Kupfer A, Burn P, Singer S J
Department of Biology, University of California, San Diego, La Jolla.
J Mol Cell Immunol. 1990;4(6):317-25.
Previous experiments with individual cell couples formed between cloned T helper (Th) cells and antigen-presenting cells have led us to suggest that the cytoskeletal protein talin may be associated with the cell surface protein LFA-1 in the Th cell. In order to examine this suggestion, we induced the surface capping of LFA-1 with suitable specific antibody reagents on the intact Th cells, and then determined by double immunofluorescence microscopic experiments, whether talin was co-clustered with the LFA-1 caps. With untreated Th cells, capping of LFA-1 did not result in any redistribution of intracellular talin. However, if the intact Th cells were treated with the phorbol ester PMA, the capping of LFA-1 resulted in a co-clustering of talin with the LFA-1 caps, but not a alpha-actinin. The capping of TCR or CD4 on the Th cells with or without pretreatment with PMA did not lead to any such co-clustering of talin with these caps. PMA treatment of the Th cells therefore induces a direct or indirect association of talin with LFA-1 underneath the Th cell surface. PMA treatment of the Th cells also increased their polarized spreading and adherence to substrata, as had been observed before. We found, furthermore, that this increased adherence upon PMA-treatment was inhibited by the presence of antibodies to LFA-1. The association of talin, and very likely also F-actin microfilaments, with LFA-1 appears to mediate a generalized increased adhesivity of the Th cells. The relevance of these findings with isolated Th cells to the interaction of Th cells with specific antigen-presenting cells is discussed.
先前利用克隆的T辅助（Th）细胞与抗原呈递细胞形成的单个细胞对进行的实验，使我们推测细胞骨架蛋白踝蛋白可能与Th细胞中的细胞表面蛋白淋巴细胞功能相关抗原-1（LFA-1）有关。为了验证这一推测，我们用合适的特异性抗体试剂在完整的Th细胞上诱导LFA-1的表面帽化，然后通过双重免疫荧光显微镜实验确定踝蛋白是否与LFA-1帽共聚集。对于未处理的Th细胞，LFA-1的帽化不会导致细胞内踝蛋白的任何重新分布。然而，如果完整的Th细胞用佛波酯PMA处理，LFA-1的帽化会导致踝蛋白与LFA-1帽共聚集，但不会与α-辅肌动蛋白共聚集。无论是否用PMA预处理，Th细胞上TCR或CD4的帽化都不会导致踝蛋白与这些帽的任何此类共聚集。因此，PMA处理Th细胞可诱导踝蛋白与Th细胞表面下方的LFA-1直接或间接结合。如之前所观察到的，PMA处理Th细胞还增加了它们的极化铺展和对基质的黏附。此外，我们发现，PMA处理后这种增加的黏附被抗LFA-1抗体的存在所抑制。踝蛋白以及很可能还有F-肌动蛋白微丝与LFA-1的结合似乎介导了Th细胞普遍增加的黏附性。本文讨论了这些关于分离的Th细胞的发现与Th细胞与特异性抗原呈递细胞相互作用的相关性。
