Cytotoxicity in Graft-versus-host Reaction

Under in vitro conditions spleen cells from nonirradiated F(1) hybrids, in which a (graft-vs.-host) (GVH) reaction had been induced with lymphoid cells of parental origin, lysed nonspecifically target cells, i.e., cells syngeneic or allogeneic to the parental genotypes. Furthermore, tumor cells exposed in vitro to spleen cells of F(1) hybrid mice undergoing GVH reaction had markedly decreased ability to grow in syngeneic recipients. Experiments involving inhibition of cytotoxicity with alloantisera indicated that this nonspecific effect was due to host cells. By contrast, spleen cells of lethally irradiated F(1) hybrids undergoing GVH reaction lysed specifically the target cells of the genotype against which the parental (donor) cells had been sensitized; this finding further supports the contribution of host cells to the nonspecific cytotoxic effects in GVH reaction. From these results it was deduced that the cytotoxic effects during GVH reaction involve at least two processes: (a) sensitization of the donor cells to the antigens of the recipient resulting in the activation of their potential to lyse specifically the recipient's cells, and (b) activation of the host's cells into a state of nonspecific cytotoxicity, as a consequence of the immunologically specific attack of the donor cells.