Regulatory role of CD8 in major histocompatibility complex-unrestricted tumoricidal activity of mouse T cells activated with anti-CD3 monoclonal antibody

Immunol Invest. Aug-Dec 1997;26(5-7):601-14. doi: 10.3109/08820139709088544.

Abstract

Antigen-nonspecific CD8+ cytotoxic T cells induced with anti-CD3 monoclonal antibody (mAb) are able to kill tumor cells in a major histocompatibility complex (MHC)-unrestricted fashion. However, the role of CD8 in the MHC-independent tumoricidal activity of anti-CD3-activated killer T (AK-T) cells has not been investigated. Here we show that anti-CD8 alpha mAb inhibits, in a dose-dependent fashion, lysis of P815 and YAC-1 tumor cells by mouse AK-T cells. The inhibition of MHC-unrestricted cytotoxicity by anti-CD8 alpha mAb cannot be attributed to interference with an adhesion-like function of CD8 towards class I MHC molecules on the target cells because anti-CD8 alpha mAb (i) had equal inhibitory effects on the cytolysis of tumor target cells regardless of their relative level of class I MHC molecule expression and (ii) did not interfere with the formation of conjugates between AK-T cells and class I MHC-bearing P815 tumor cells. However, anti-CD8 alpha mAb abrogated AK-T cell granule exocytosis in the presence of P815 tumor cells, indicating a regulatory role for CD8 in the signal transduction events which result in lysis of the tumor target cells. Immunoblot analysis of the post-nuclear fraction of lysates from AK-T cells exposed to P815 tumor cells in the presence of anti-CD8 alpha mAb revealed reduced phosphorylation of tyrosine residues on a protein with an Mr of approximately 62 kDa. Taken together, these data suggest that CD8 is able to affect the tumoricidal activity of MHC-unrestricted AK-T cells independent of class I MHC molecules on the target cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • CD8 Antigens / immunology*
  • CD8 Antigens / pharmacology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic / drug effects
  • Cytotoxicity, Immunologic / immunology*
  • Down-Regulation
  • Female
  • Lymphocyte Activation
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Proteins / metabolism
  • Spleen / cytology

Substances

  • Antibodies, Monoclonal
  • CD8 Antigens
  • Proteins