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 reactivity against porcine stimulator cells, purified CD4+ and CD8+ human peripheral T lymphocytes have been tested for their responsiveness against 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-1α, IL-1β, or IL-6. Production of IL-2 was not detected in the xenostimulated CD8+ responder cells, nor could IL-2 production be restored by the addition of IL-1α, IL-1β, or IL-6. The presence of human CD4+ responder cells was crucial both for a xenoproliferative response and for IL-2 synthesis. However, when the expression of the IL-2 receptor (CD25) on the CD8+ T cells was analyzed, no difference was detected 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 in xenogeneic MLR was significantly lower than that in the allogeneic combination. In the xenogeneic combination, exogenous IL-2 reconstituted the cytotoxicity by purified CD8+ T cells; however, IL-1α, IL-1β, or IL-6 did not. Our results show that purified human CD4+ T cells respond directly against pig PBMCs, whereas purified CD8+ T cells do not. Furthermore, responsiveness in CD8+ T cells is completely restored by the addition of human IL-2.