Mitogen-induced lymphocyte-mediated cytotoxicity in vitro: effect of mitogens selectively activating T or B cells.

Abstract

AbstractConcanavalin A (Con A) and phytohemagglutinin (PHA) are selective T cell mitogens, whereas lipopolysaccharide (LPS) and purified protein derivative of tuberculin (PPD) are selective B cell mitogens. Con A and PHA induced mouse lymphocyte‐mediated cytotoxicity in vitro, which was equally expressed on autologous, allogeneic and heterologous target fibroblasts, as measured by thymidine release from prelabeled targets. The dose response curves of Con A‐induced lymphocyte‐mediated cytotoxicity and DNA synthesis were parallel, 5 μg/ml being optimal, both higher and lower concentrations being less effective. Con A pretreated mouse lymphocytes failed to express cytotoxicity even though they were irreversibly activated with regard to DNA synthesis and were morphologically transformed. However, when Con A pretreated lymphocytes were added to target fibroblasts in the presence of soluble Con A, the cytotoxic effect markedly exceeded that induced by Con A in non‐pretreated lymphocytes. It is suggested that cytotoxicity not only requires close contact between target and aggressor lymphocyte, but actual binding of the lymphocyte to the target, in this case effectuated by Con A.Con A and PHA failed to induce lymphocyte‐mediated cytotoxicity in B lymphocytes. LPS and PPD did not induce cytotoxicity in normal or in B lymphccytes. Even LPS or PPD pretreated B lymphocytes failed to exert cytotoxicity when aggregated to the targets by Con A. It is suggested that the lymphocytes responsive to LPS and PPD are not the non‐T cells responsible for cell‐mediated cytotoxicity on antibody‐coated target cells.Con A and PHA, but not LPS and PPD, induced lymphocyte‐mediated cytotoxicity in human lymphocytes on allogeneic and heterologous target fibroblasts. The dose response curves for induction of cytotoxicity and DNA synthesis by Con A were not always identical in this case, cytotoxicity persisting at low Con A concentrations, which failed to activate DNA synthesis.