A number of observations have suggested that host lymphocytes, specifically cytotoxic T cells (CTL) may play a significant role in mediating allogeneic marrow graft rejection. In a murine model system, CTL were cloned from the spleens of sublethally irradiated animals which had rejected MHC disparate marrow grafts. It was found that cloned CTL were sufficient to effect rejection of T cell depleted allogeneic marrow in lethally irradiated animals. The rejection of marrow grafts by CTL was specific for the MHC gene products expressed by the marrow cells and correlated with the cytotoxic specificity of the individual clones. Because host CTL in isolation could reject donor marrow grafts, effects on engraftment by (1) cell populations able to suppress host CTL responses, and (2) the administration of anti-CD3 monoclonal antibody in vivo, which by previous work had been shown to suppress CTL function, were studied. Cells with a specific type of suppressor activity, termed veto cells, which might suppress host rejection responses, have been reported to be present in marrow. The ability of IL-2 to enhance the activity of veto suppressor cell populations remaining in marrow after T cell depletion was investigated in vitro and in vivo. It was found that the incubation of T cell depleted marrow with IL-2 significantly increased veto activity as assessed by in vitro assays and also enhanced engraftment of MHC-mismatched, T cell depleted marrow in vivo, and that veto cells exerted their effect by clonal deletion of precursor CTL. In further studies of engraftment of T cell depleted allogeneic marrow, host mice were treated with anti-CD3 monoclonal antibody. Marked enhancement of engraftment was observed; this effect on engraftment was enduring and due to suppression of host T cell function and to the release of multiple cytokines associated with in vivo activation of T cells by anti-CD3 antibody.
