MURINE APC ACTIVATION IN THE XENOGENEIC MLC

Purified human T cells proliferate in response to direct and indirect presentation of human alloantigens. However, until recently it was bel ieved that human T cells could respond only indirectly to murine xenoa ntigens. We recently used the mixed leucocyte culture (MLC) to demonst rate that purified human T cells proliferate in response to direct pre sentation of murine xenoantigens by murine antigen-presenting cells (A PC) in the presence of human cytokines. We suggested that cytokines mi ght function poorly across species barriers. In this study, we demonst rate that although proliferation occurs in the presence of exogenously added cytokines, the precursor frequency of responding human T cells is much tower in a xenogeneic than in an allogeneic MLC. We demonstrat e that human T cells also proliferate in response to murine APC in the presence of murine cytokines, and murine cytokines augment the prolif erative response seen in a human anti-human MLC, ruling out the possib ility that an absolute cytokine incompatibility exists between these s pecies. We show that exogenously added human IL-1 causes maximal proli feration of human T cells in response to murine xenoantigens only when added early in the culture. We further demonstrate that murine APC pr eincubated in human rIL-1, and washed extensively, prior to use as sti mulating cells, cause human T-cell proliferation without the need for exogenously added cytokines. Finally, we noted that during interaction s of human T cells and murine APC, little to no IL-1 is produced, wher eas after the addition of exogenous IL-1, a marked increase in the pro duction of IL-1 is seen. These data suggest that during interactions b etween human T cells and murine APC, the murine cells do not receive a dequate stimulation to produce sufficient costimulatory signals to all ow proliferation of the human T cells.