Green J M, Zheng X G, Shimizu Y, Thompson C B, Turka L A
Department of Internal Medicine and Microbiology, University of Michigan Medical Center, Ann Arbor 48109.
Eur J Immunol. 1994 Jan;24(1):265-72. doi: 10.1002/eji.1830240141.
Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge. In this manuscript we specifically examine the role of two accessory molecules, CD28 and LFA-1, in modulating the T cell proliferative response to a variety of stimuli. We demonstrate that the proliferation induced by staphylococcal enterotoxins A and B in combination with CD28 costimulation is dependent on LFA-1-mediated events. This requirement for LFA-1 is independent of T cell-accessory cell adhesion. Similarly, an allogeneic mixed lymphocyte reaction, which has previously been shown to be a CD28-dependent response, can be inhibited by blockade of LFA-1. This suggests LFA-1 plays an essential role in these responses, either by enhancing intercellular adhesion or by an independent signal transduction event. In contrast, when the primary activating stimulus is delivered by immobilized anti-CD3 antibody or by PMA, and the secondary stimulus by either alpha-CD28 or cell-bound CD28 ligand B7, there is no requirement for LFA-1. In addition, we demonstrate that cross-linking of LFA-1 with immobilized monoclonal antibody, or engagement of LFA-1 with ICAM-1 expressed on the surface of a CHO cell, provide an insufficient costimulus for T cell proliferation initiated by enterotoxin, immobilized alpha-CD3 or phorbol ester. Our data suggests that LFA-1, in contrast to CD28, functions not as a costimulatory molecule, but serves primarily to modulate the signal delivered through the T cell receptor.
辅助分子在T细胞对抗抗原刺激的应答发育过程中发挥着关键作用。在本论文中，我们专门研究了两种辅助分子CD28和淋巴细胞功能相关抗原-1（LFA-1）在调节T细胞对多种刺激的增殖应答中的作用。我们证明，葡萄球菌肠毒素A和B与CD28共刺激联合诱导的增殖依赖于LFA-1介导的事件。对LFA-1的这种需求独立于T细胞-辅助细胞黏附。同样，先前已证明是CD28依赖性应答的同种异体混合淋巴细胞反应可被LFA-1的阻断所抑制。这表明LFA-1在这些应答中发挥着重要作用，要么通过增强细胞间黏附，要么通过独立的信号转导事件。相比之下，当主要激活刺激由固定化抗CD3抗体或佛波酯（PMA）提供，次要刺激由α-CD28或细胞结合的CD28配体B7提供时，则不需要LFA-1。此外，我们证明，用固定化单克隆抗体使LFA-1交联，或使LFA-1与CHO细胞表面表达的细胞间黏附分子-1（ICAM-1）结合，对于由肠毒素、固定化α-CD3或佛波酯引发的T细胞增殖提供的共刺激不足。我们的数据表明，与CD28不同，LFA-1不作为共刺激分子发挥作用，而是主要用于调节通过T细胞受体传递的信号。
