Allo-skin graft rejection, tumor rejection and natural killer activity in mice lacking p56lck

Eur J Immunol. 1995 Nov;25(11):3155-9. doi: 10.1002/eji.1830251125.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Graft Rejection / immunology*
  • Immunologic Surveillance / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Neoplasm Transplantation / immunology
  • Neoplasms, Experimental / immunology
  • Skin Transplantation / immunology
  • Transplantation, Homologous / immunology
  • src-Family Kinases / deficiency*
  • src-Family Kinases / genetics

Substances

  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases