Monoclonal antibodies (G1.4, D7.5) induce secretion of lytic factors from natural killer and T lymphocytes.

Abstract

Monoclonal antibodies were made by standard procedures using mononuclear cells isolated from hamster lung tissue to immunize the mice. The Moabs (G1.4, D7.5), secreted by the selected hybridomas, were isotyped as IgG2a, Kappa and were lytic in the presence of complement for 20% lymphocytes from lymph nodes or lung tissue; 40-50% of lymphocytes from spleen or bone marrow; and 70-80% of thymocytes or nylon wool nonadherent lung or lymph node lymphocytes. Functional studies showed that prior incubation of either Moab with enriched natural killer (NK) and T lymphocyte subpopulations did not interfere with effector:target conjugate formation but did block the ability of the effector cells to lyse NK-sensitive targets. We conclude that the Moabs bind to a molecule(s) on NK and T lymphocytes. Further, the preincubation medium acquired the capacity to lyse preferentially NK-sensitive targets but not NK-insensitive targets. Interestingly, the Moabs were able to induce secretion of lytic factors from thymocytes and to induce resting peripheral T lymphocytes to acquire NK activity and release lytic factors. The ability of the Moab to signal release of lytic factors was retained even when monovalent Fab fragments were used; therefore, the Moabs initiate secretion by mechanisms that do not apparently involve crosslinking or Fc receptor interaction. G1.4 and D7.5 Moabs were functionally and antigenically crossreactive with human, rat, and hamster lymphocytes but not with mouse lymphocytes. Biochemical and immunochemical analysis showed that the G1.4 and D7.5 antigen on thymus cells and lung mononuclear cells has an apparent molecular weight of 27 kD. Although it is unlikely that there is an universal mechanism for secretion used by cells in general, it is interesting that Moab treatment of three different subpopulation of lymphocytes induced secretion of lytic factors and suggests that under physiologic conditions a common molecule might participate in induction of the secretion pathway. These studies lead to the hypotheses that 1) NK and T lymphocytes share a cell surface molecule that participates in signals that initiate secretion and that 2) the expression of the G1.4, D7.5 antigens precedes thymic differentiation.