Blastogenic responses of human lymphocytes to xenogeneic cells in vitro

The blastogenic responses of human lymphocytes to stimulation with irradiated xenogeneic cultured cells and xenogeneic lymphocytes were compared to responses to allogeneic cultured lymphoblasts and lymphocytes. Xenogeneic cultured cells stimulated vigorous blastogenesis as measured by either thymidine incorporation (median, 13,500 counts/min) or microscopic examination (median, 12% lymphoblasts). Maximum stimulation was induced by 5 X 104 xenogeneic cultured cells and levels of over 10° stimulator cells/culture inhibited blastogenesis. Xenogeneic lymphocytes induced a median maximum of 14,000 counts/min at a stimulator cell concentration of 10° cells/culture. Allogeneic cultured lymphoblasts and lymphocytes induced significantly greater blastogenic responses (median, 57,000 and 41,000 counts/min, respectively) but were also inhibitory at higher cell concentrations. Cultured cells, both allogeneic and xenogeneic, induced more uniform stimulation than small lymphocytes. These results indicate that humans have circulating antigen-reactive cells for murine cell surface antigens, that there are major quantitative differences in the characteristics of the stimulation produced by cells of different origin in terms of degree of stimulation and optimal stimulator cell level, and that irradiated cells release an inhibitor of blastogenesis.