Hafler D A, Chofflon M, Benjamin D, Dang N H, Breitmeyer J
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
J Immunol. 1989 Apr 15;142(8):2590-6.
The Ta1 (CDw26) Ag distinguishes a subset of circulating T lymphocytes that is the major population proliferating to recall Ag challenge. Unlike receptors for growth factors such as IL-2 and transferrin, the Ta1 Ag is present on T cell lines and clones irrespective of cell cycle. The appearance of Ta1 on T cells that respond to recall Ag allowed us to investigate activation requirements that may be associated with T cell immune memory. Ta1+ peripheral blood T cells were induced to proliferate by mAb recognizing either the invariant chains of the TCR, or by pairs of mitogenic antibodies directed to the CD2 molecule. In contrast, Ta1- cells were not stimulated by these antibodies. In addition, Ta1-cells did not proliferate maximally after addition of the phorbol ester PMA in combination with the calcium ionophore Ionomycin, suggesting that the intracellular targets of these agents may not be fully active. Anti-CD3-induced elevation of intracellular calcium levels was equivalent in the two subpopulations, suggesting that calcium mobilization mechanisms were intact. In contrast, PMA-induced phosphorylation of TCR CD3 chains was significantly greater in Ta1+ cells as compared to Ta1- T cells. Taken together, our results indicate that Ta1 expression, which is associated with T cell activation and memory, may be causally related to TCR and CD2-mediated activation mechanisms. The PMA inducible TCR phosphorylation in Ta1+ memory cells associated with their increased ability to proliferate after CD3/TCR or CD2 stimulation suggests that intracellular phosphorylation events may be causally associated with T cell immune memory.
Ta1(CDw26)抗原可区分循环T淋巴细胞的一个亚群,该亚群是对回忆抗原刺激进行增殖的主要细胞群体。与白细胞介素-2和转铁蛋白等生长因子的受体不同,Ta1抗原存在于T细胞系和克隆中,与细胞周期无关。对回忆抗原产生反应的T细胞上Ta1的出现,使我们能够研究可能与T细胞免疫记忆相关的激活需求。识别TCR恒定链的单克隆抗体,或针对CD2分子的有丝分裂抗体对,可诱导Ta1 +外周血T细胞增殖。相比之下,这些抗体不能刺激Ta1 -细胞。此外,在添加佛波酯PMA与钙离子载体离子霉素后,Ta1 -细胞不会最大程度地增殖,这表明这些药物的细胞内靶点可能未完全激活。两个亚群中抗CD3诱导的细胞内钙水平升高相当,表明钙动员机制是完整的。相比之下,与Ta1 - T细胞相比,Ta1 +细胞中PMA诱导的TCR CD3链磷酸化明显更高。综上所述,我们的结果表明,与T细胞激活和记忆相关的Ta1表达可能与TCR和CD2介导的激活机制存在因果关系。Ta1 +记忆细胞中PMA诱导的TCR磷酸化与其在CD3/TCR或CD2刺激后增殖能力的增强相关,这表明细胞内磷酸化事件可能与T细胞免疫记忆存在因果关系。