Allo-skin graft rejection, tumor rejection and natural killer activity in mice lacking p56lck.
Mice lacking the p56lck molecule (lck -/-) have a profound block in the maturation of thymocytes and a greatly reduced number of peripheral mature T cells. To analyze further the functions of the T cells developed in lck -/- mice in vivo, we evaluated the ability of lck -/- mice to reject allo-skin grafts and methylcholanthrene (MCA)-induced syngeneic fibrosarcoma, and also examined the biological activity of lck -/- natural killer (NK) cells. Mice lacking p56lck failed to reject skin grafts from either MHC-disparate or minor-histocompatibility-different donors, even after they had been primed with donor spleen cells. They also failed to reject the MCA-induced immunogenic syngeneic fibrosarcoma, MC57X. NK activity in mice lacking p56lck was normal, and there were no differences in the NK cell activation induced by poly(I).poly(C) stimulation or interleukin-2 stimulation (lymphokine-activated killer induction) between mice lacking p56lck and their immunocompetent heterozygous littermates. NK cells lacking p56lck mediated a normal antibody-dependent cell-mediated cytotoxicity (ADCC) response. The results of this study indicate that the loss of p56lck severely impairs the effectors of the immune system which mediate the rejection of allo-skin grafts and syngeneic tumors. The normal NK activity in lck -/- mice suggests that p56lck is not required for the development and activation of NK cells.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007157:Immunologic Surveillance / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009368:Neoplasm Transplantation / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology; D019061:src-Family Kinases / Q000172:deficiency* / Q000235:genetics
D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases