HUMAN CD8 RESPONDER CELLS CAN BE DIRECTLY ACTIVATED TO PROLIFERATE AND TO PRODUCE IL-2 FOLLOWING STIMULATION BY ALLOGENEIC, BUT NOT BY XENOGENEIC, PORCINE BLOOD MONONUCLEAR-CELLS

In order to determine the precise nature of human T lymphocytes reacti vity against porcine stimulator cells, purified CD4+ and CD8+ human pe ripheral T lymphocytes have been tested for their responsiveness again st porcine stimulator cells. In a xenogeneic mixed lymphocyte reaction (MLR), CD4+ T cells were capable of proliferating as a result of the recognition of porcine peripheral blood lymphocytes (PBL), whereas CD8 + T cells were unresponsive. A proliferative response of CD8+ T cells could be restored by treatment with human IL-2, but not by IL-1 alpha, IL-1 beta, or IL-6. Production of IL-2 was not detected in the xenost imulated CD8+ responder cells, nor could IL-2 production be restored b y the addition of IL-1 alpha, IL-1 beta, or IL-6. The presence of huma n CD4+ responder cells was crucial both for a xenoproliferative respon se and for IL-2 synthesis. However, when the expression of the IL-2 re ceptor (CD25) on the CD8+ T cells was analyzed, no difference was dete cted between xenostimulated and allostimulated CD8+ T cells, When the development of cytotoxic T cells in xenogeneic and allogeneic MLRs was compared, the cytotoxic activity exhibited by purified CD8+ T cells i n xenogeneic MLR was significantly lower than that in the allogeneic c ombination. In the xenogeneic combination, exogenous IL-2 reconstitute d the cytotoxicity by purified CD8+ T cells; however, IL-1 alpha, IL-1 beta, or IL-6 did not, Our results show that purified human CD4+ T ce lls respond directly against pig PBMCs, whereas purified CD8+ T cells do not. Furthermore, responsiveness in CD8+ T cells is completely rest ored by the addition of human IL-2.