ALLO-SKIN GRAFT-REJECTION, TUMOR REJECTION AND NATURAL-KILLER ACTIVITY IN MICE LACKING P58(LCK)

Mice lacking the p56(lck) 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 p56(lck) 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 p56(lck) 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 p56(lck) and their immunocompetent heterozygous littermates. NK cells lacking p56(lck) mediated a normal antibody-dependent cell-mediated cytotoxicity (ADCC) response. The results of this study indicate that the loss of p56(lck) 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 p56(lck) is not required for the development and activation of NK cells.