This project is a study of natural and induced resistance of mice to the proliferation of hemopoietic tumors. The investigations are focused on the immunobiology and heterogeneity of effector systems; on regulatory mechanisms, and on genetic controls of responsiveness, target determinants, and differentiation of effector and regulatory cell populations. The identity of hemopoietic-histocompatibility (Hh) and/or major histocompatibility complex (H-2) gene products expressed on normal hemopoietic stem cells and leukemia-lymphoma cells is central to the project since recognition of these structures by cells of the lymphoid system leads to inhibition and/or rejection of target cells in vivo (i.e., hybrid and allogeneic resistance) and to cytotoxicity in vitro (i.e., primary F?1? antiparent cell-mediated lympholysis). Emphasis will be placed not only on Hh/H-2-controlled structures but also on other cellular structures that serve as targets for mouse reactivities against autologous or syngeneic tumors. Such """"""""autoreactivities"""""""" are mediated by effectors belonging to the natural killer (NK) and cytotoxic T lymphocyte (CTL) classes. Resistance to parental lymphoma grafts by irradiated F?1? hybrid mice involves unidentified effector mechanisms, in part NK-like (effectors need not be induced and are relatively radioresistant, thymus independent, modulated by interferon), yet recognizing specific Hh/H-2 gene products and causing graft rejection within 18 to 96 hrs. The in vitro activation of F?1? antiparent CTL involves different mechanisms, since responder cells must be stimulated and are radiosensitive as well as thymus dependent. F?1? antiparent CTL recognize the products of genes that are indistinguishable from Hh genes in certain haplotypes and strains but are distinguishable in others according to recombinant analysis. (LB)
