Regulatory role of CD8 in major histocompatibility complex-unrestricted tumoricidal activity of mouse T cells activated with anti-CD3 monoclonal antibody.
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.
Stewart
B H
BH
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Hoskin
D W
DW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D016827:CD8 Antigens / Q000276:immunology* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D011506:Proteins