Abrogation of the lethal graft‐vs.‐host reaction developed to non‐H‐2 antigens: involvement of T suppressor cells distinct from veto cells

摘要

AbstractThe mortality induced by graft‐vs.‐host reaction (GVHR) in (DBA/2 × B10.D2)F1recipients transplanted with cells from H‐2d‐identical B10.D2 donors can be abrogated by preimmunizing the donors with parent‐strain spleen cells from normal DBA/2 mice. The experiments described here were designed to explore the possibility that the observed protection might be mediated by veto cells contained in the immunizing cell inoculum; the reasoning was based on an analogy with the cytotoxic T lymphocyte response to non‐H‐2 antigens where suppression can be mediated by veto cells, present in the spleens of normal mice, which are radiosensitive and largely Lyt‐2+. We show that the intensity of the protection against GVHR mortality is a function of the immunizing cell dose, and that protection remains effective when optimal doses of immunizing cells are (a) irradiated or (b) pretreated with anti‐Thy‐1 serum. GVHR suppression is abrogated when, before transfer to F1recipients, suppressor cells from spleens of immunized donors are pretreated with antiserum directed against Lyt‐1.2 (expressed by B10.D2 but not by DBA/2, which expresses Lyt‐1.1); in contrast, it is not significantly affected when these same cells are pretreated with anti‐Lyt‐2.2 alloantiserum. We conclude that when the antigen load is great enough the immunizing cells play a largely passive role in the observed suppression. The protection against GVHR mortality seen in this H‐2‐compatible combination is transferable by Lyt‐1+2−suppressor T cells originating in mice given high doses of alloantigen. These suppressor cells are therefore distinct from the splenic veto T cells effective against cytotoxic T lymphocyte responses to non‐H‐2 antigens. The mechanism of the observed suppression and its rela