Antigen-dependent release of IFN-gamma by cytotoxic T cells up-regulates Fas on target cells and facilitates exocytosis-independent specific target cell lysis.
Effector cytolytic T (Tc) lymphocytes, deficient in the exocytosis-mediated pathway of target cell lysis, induce Fas on target cells and, in turn, delayed cell death and apoptosis via the Fas ligand-Fas interaction. The induction of Fas can be blocked by anti- IFN-gamma Abs. This Fas up-regulation on initially Fas-negative target cells is not mediated by TCR-MHC/peptide signaling per se, but by secreted IFN-gamma from Tc cells after Ag engagement. The Fas up-regulation by Tc cells can be mimicked by treatment of target cells with rIFN-gamma. Tc cells from IFN-gamma knockout mice do not induce Fas expression on target cells. Tc cell-mediated Fas expression on third party, bystander, target cells does not enhance their susceptibility to lysis by these nominal effector cells. The results are discussed as to the possible relevance of the phenomenon in efficiency and regulation of the Tc cell response to infections by viruses.
Müllbacher
Arno
A
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia. arno.mullbacher@anu.edu.au
Lobigs
Mario
M
Hla
Ron Tha
RT
Tran
Thao
T
Stehle
Thomas
T
Simon
Markus M
MM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D024201:Bystander Effect / Q000276:immunology; D002860:Chromium Radioisotopes / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004247:DNA / Q000037:antagonists & inhibitors; D053938:DNA Fragmentation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005089:Exocytosis / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000502:physiology*; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007739:L Cells; D007939:Leukemia L1210; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis* / Q000502:physiology
D000911:Antibodies, Monoclonal; D002860:Chromium Radioisotopes; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D019014:fas Receptor; D054353:Perforin; D007371:Interferon-gamma; D004247:DNA; D012697:Serine Endopeptidases