Goldstein J S, Chen T, Brunswick M, Mostowsky H, Kozlowski S
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
J Immunol. 1998 Apr 1;160(7):3180-7.
T cells play a central role in the initiation, maintenance, and regulation of the immune response. Effector responses of T cells are controlled by complex combinations of lymphokines and adhesion/costimulatory molecule signals. To isolate the effects of specific adhesion/costimulatory molecules and to define the minimal molecular requirements of naive CD8+ T cell activation, we have developed an APC-free system for stimulation of naive CD8+ T cells. In this report, we demonstrate that immobilized MHC class I-peptide complexes can activate naive CD8+ T cells from TCR transgenic mice at low cell densities. The CD8+ T cells were stimulated to proliferate and secrete IL-2 independently of the molecular interactions between CD28/B7.1-B7.2 or LFA-1/ICAM-1 surface receptors. Previous reports have shown that CD28 ligation is necessary for late T cell survival of APC-stimulated naive CD8+ T cells. Our data suggest that under certain specific conditions of high intensity T cell signaling, early activation and late cell proliferation can occur independently of APC-derived costimulatory signals.
T细胞在免疫反应的启动、维持和调节中发挥核心作用。T细胞的效应反应受淋巴因子和黏附/共刺激分子信号的复杂组合控制。为了分离特定黏附/共刺激分子的作用并确定初始CD8 + T细胞活化的最小分子要求，我们开发了一种无抗原呈递细胞（APC）的系统来刺激初始CD8 + T细胞。在本报告中，我们证明固定化的MHC I类肽复合物能够在低细胞密度下激活TCR转基因小鼠的初始CD8 + T细胞。CD8 + T细胞被刺激增殖并分泌IL-2，这与CD28/B7.1 - B7.2或LFA-1/ICAM-1表面受体之间的分子相互作用无关。先前的报告表明，CD28连接对于APC刺激的初始CD8 + T细胞的晚期T细胞存活是必要的。我们的数据表明，在高强度T细胞信号传导的某些特定条件下，早期活化和晚期细胞增殖可以独立于APC衍生的共刺激信号而发生。
