Induction of anti-CD8 resistant cytotoxic T lymphocytes by anti-CD8 antibodies. Functional evidence for T cell signaling induced by multi-valent cross-linking of CD8 on precursor cells.
The effector function of most MHC class I allospecific CTL is inhibited by anti-CD8 mAb. In the present study, we report the surprising observation that multi-valent cross-linking of CD8 molecules on precursor cells by specific antibody actively induces the generation of CD8+ class I allospecific CTL whose lytic function is resistant to anti-CD8 antibody inhibition, and actively induces down-modulation of cell surface CD8 expression on these cells. In marked contrast, bi-valent cross-linking of CD8 inhibits the generation of CD8+ CTL from precursor cells and fails to induce down-modulation of cell surface CD8 expression. These results demonstrate that CD8 can transduce net positive signals, but only when the molecule is extensively cross-linked.
McCarthy
S A
SA
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Kaldjian
E
E
Singer
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001667:Binding, Competitive; D016827:CD8 Antigens; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D015398:Signal Transduction; D013234:Stem Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I