Lymphocyte-mediated cytotoxicity in vitro. Effect of enhancing antisera.

ABSTRACT

The ability of antisera to suppress immune responses either in vivo or in vitro is well known. A variety of lymphocyte-target cell systems have been employed to demonstrate inhibition of cell-mediated immunity by antisera in vitro, and skin, tumor, and kidney graft survival have been prolonged by passively administered antiserum in vivo. An in vitro lymphocyte-tumor cell assay system was developed for the purpose of studying the effects of enhancing antisera (in vivo) on lymphocyte-mediated cytotoxicity in vitro. The characteristics of this system with respect to route of immunization, time of harvest of immune cells, lymphocytetumor cell ratio, and effect of nonimmune or nonspecifically immune lymphoid cells are presented. Sera capable of enhancement in vivo were tested in this system and shown to inhibit cell-mediated immunity in vitro. Further, in both instances the immunosuppressive effect is mediated by antigen-antibody complexes and not by free antibody alone. Experiments were also carried out to determine the site of action of these suppressive antigen-antibody complexes. Presensitized lymphocytes were exposed to antigen-antibody complexes, washed, and then allowed to interact with fresh tumor cells (not antibody treated). Lymphocytes treated in this manner are incapable of exhibiting cell-mediated immunity in vitro. This evidence supports the concept that the antigen-antibody complexes have a direct immunosuppressive effect on the lymphocyte.