Spontaneous in vivo retrovirus-infected T and B cells, but not dendritic cells, mediate antigen-specific Fas ligand/Fas-dependent apoptosis of anti-retroviral CTL.
C57BL/6 (H-2b), but not spontaneous virus-expressing AKR.H-2b congenic, mice generate retrovirus-specific CD8+ CTL responses to the immunodominant Kb-restricted epitope, KSPWFTTL. AKR.H-2b non-responsiveness is mediated by a peripheral tolerance mechanism. When co-cultured with primed B6 antiviral pCTL, AKR.H-2b splenocytes are recognized by the antiviral TcR as "veto" cells, which inhibit by an exquisitely virus-specific, MHC-restricted, veto cell FasL/responder T cell Fas, mediated apoptotic mechanism. Here, AKR.H-2b thymus, lymph node, and bone marrow cells are also shown to inhibit antiviral CTL generation. Purified AKR.H-2b CD4+ and CD8+ T cells, and B cells, served effectively as FasL-dependent veto cells. In contrast, AKR.H-2b dendritic cells (DC) did not efficiently veto antiviral CTL responses, despite expressing sufficient MHC class I/viral peptide complexes for TcR recognition. AKR.H-2b DC also expressed FasL mRNA and cell surface protein, albeit at a lower level than AKR.H-2b T and B cells. These findings suggest a fail-safe escape mechanism by virus-infected cells for escape from CTL-mediated immunity.
Rich
Robert F
RF
Department of Microbiology and Immunology and the Norris Cotton Cancer Center, Dartmouth Medical School, 1 Medical Center Drive, Borwell 603 West, Lebanon, New Hampshire 03756, USA.
Cook
W James
WJ
Green
William R
WR
D000406:AKR murine leukemia virus / Q000276:immunology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015870:Gene Expression; D006183:H-2 Antigens / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D000956:Antigens, Viral; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D019014:fas Receptor