Bellio M, Leal L M, Scharfstein J, Dos Reis G A
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Brazil.
Cell Immunol. 1991 Jul;135(2):534-40. doi: 10.1016/0008-8749(91)90296-n.
Resting murine T cell activation induced by either CD3 complexes or Thy1 molecules was investigated in vitro, using surface-bound anti-CD3 mAb as the stimulus. One mitogenic anti-Thy 1 mAb (G7) lost mitogenicity when presented to T cells immobilized on a plastic surface, even in the presence of phorbol ester. Moreover, T cell activation induced by immobilized anti-CD3 was potently blocked by coimmobilized anti-Thy 1 mAb. Nonmitogenic anti-Thy 1 mAb also blocked CD3-induced activation when coimmobilized with anti-CD3. Control experiments showed that anti-Thy 1 specifically blocked T cell activation, even in the presence of measurable and functional concentrations of plastic-bound anti-CD3. Coimmobilized anti-Thy 1 potently blocked IL2 secretion stimulated by anti-CD3. Addition of exogenous rIL2 completely prevented anti-Thy 1-mediated blockade. On the other hand, while completely blocking T cell proliferation, immobilized anti-Thy 1 only partially blocked secretion of IL3-like activity by the T cells. One IgM anti-Thy 1 mAb (2A3) induced secretion of IL3-like activity by T cells when immobilized in the absence of bound anti-CD3. These results indicate that extensive aggregation of Thy 1 molecules delivers a potent negative signal which antagonizes CD3-mediated T cell activation and growth.
利用表面结合的抗CD3单克隆抗体作为刺激物，在体外研究了由CD3复合物或Thy1分子诱导的静止小鼠T细胞活化。一种促有丝分裂的抗Thy 1单克隆抗体（G7），当作用于固定在塑料表面的T细胞时会失去促有丝分裂活性，即使在存在佛波酯的情况下也是如此。此外，固定化抗CD3诱导的T细胞活化会被共固定化的抗Thy 1单克隆抗体强烈阻断。当与抗CD3共固定化时，非促有丝分裂的抗Thy 1单克隆抗体也会阻断CD3诱导的活化。对照实验表明，抗Thy 1特异性地阻断T细胞活化，即使在存在可测量且有功能浓度的塑料结合抗CD3的情况下也是如此。共固定化的抗Thy 1强烈阻断抗CD3刺激的IL2分泌。添加外源性重组IL2完全阻止了抗Thy 1介导的阻断。另一方面，虽然固定化抗Thy 1完全阻断T细胞增殖，但仅部分阻断T细胞分泌IL3样活性。一种IgM抗Thy 1单克隆抗体（2A3）在不存在结合的抗CD3的情况下固定时，可诱导T细胞分泌IL3样活性。这些结果表明，Thy 1分子的广泛聚集传递了一个强大的负信号，该信号拮抗CD3介导的T细胞活化和生长。
