INTERACTIONS BETWEEN CD3 AND THY1 T-CELL ACTIVATION PATHWAYS - BLOCKADE OF CD3-MEDIATED LYMPHOCYTE-T ACTIVATION INDUCED BY IMMOBILIZED ANTI-THY1 ANTIBODIES

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-Thy1 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-Thy1 mAb. Nonmitogenic anti-Thy1 mAb also blocked CD3-induced activation when coimmobilized with anti-CD3. Control experiments showed that anti-Thy1 specifically blocked T cell activation, even in the presence of measurable and functional concentrations of plastic-bound anti-CD3. Coimmobilized anti-Thy1 potently blocked IL2 secretion stimulated by anti-CD3. Addition of exogenous rIL2 completely prevented anti-Thy1-mediated blockade. On the other hand, while completely blocking T cell proliferation, immobilized anti-Thy1 only partially blocked secretion of IL3-like activity by the T cells. One IgM anti-Thy1 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 Thy1 molecules delivers a potent negative signal which antagonizes CD3-mediated T cell activation and growth. © 1991.