On the Relation of Products of Activated Lymphocytes to Cell-Mediated Cytolysis

Abstract

Experiments have been designed to test the hypothesis that soluble mediator production and T-cell-mediated cytotoxicity are necessarily related phenomena, and that soluble mediators may be involved in the mechanism of cytolysis. To this end, agents known to inhibit T-cell-mediated lysis in vitro have been studied for their effects on the production of two lymphocyte-derived mediators, lymphotoxin (LT) and migration inhibitory factor (MIF). A clear dissociation between mediator production and cell-mediated cytolysis was found using inhibitors of protein synthesis. Pactamycin and emetine, in doses of 10–7 M to 10–6 M, suppressed production of MIF and LT with only slight effect on killing of mastocytoma cells by immune T cells. On the other hand colchicine and vinblastine inhibited T-cell-mediated cytolysis in a dose-related manner but had no significant effect on either MIF or LT production, A striking dichotomy was also observed after augmentation of intracellular cyclic 3'5' adenosine monophosphate (cAMP) levels with cholera enterotoxin. Increased cAMP levels were associated with abrogation of direct lytic activity, but were without significant effect on MIF or LT production in guinea pigs or mice. These findings indicate that mediator production and direct lymphocyte-mediated cytolysis can be experimentally dissociated and represent independent cell-mediated immune functions.

Changes in the Surface of Virus‐Infected Cells Recognized by Cytotoxic T Cells

“…Since protein synthesis is known to be necessarj' for the function of cytotoxic T cells (9), it was necessar)-to use an inhibitor of protein synthesis that was irreversible in its action, so that excess inhibitor could be washed out of the system before immune spleen cells were added-Pactamycin inhibits the process of initiation of protein synthesis (10) and at high concentrations prevents the translocation event (23). It has also been reported (18) to be largely irreversible in its action. This was confirmed as follows.…”

Experimental Models for Prevention of Graft-versus-Host Reaction in Bone Marrow Transfusion

“…This may be due to a dissociated development of delayed hypersensitivity against cellular antigens, accompanied by competitive suppression of cytotoxicity against the same antigens. This explanation seems plausible since Tigelaar and Gorczynski [22] have reported that delayed hypersensitivity and cytotoxicity are mediated by distinct subpopulations of T cells and Henney et al [8] have reported that T cell-mediated cytolysis and production of chemical mediators can be dissociated by the use of inhibitors of protein synthesis.…”

Experimental Models for Prevention of Graft-versus-Host Reaction in Bone Marrow Transfusion

“…This may be due to a dissociated development of delayed hypersensitivity against cellular antigens, accompanied by competitive sup-pression of cytotoxicity against the same antigens. This explanation seems plausible since Tigelaar and Gorczynski [22] have reported that delayed hypersensitivity and cytotoxicity are mediated by distinct subpopulations of T cells and Henney et al [8] have reported that T cell-mediated cytolysis and production of chemical mediators can be dissociated by the use of inhibitors of protein synthesis.…”