CD4-CD8+ T lymphocytes mediate AKR/gross murine leukemia virus nonresponsiveness in moderately aged AKR.H-2b:Fv-1b mice.
Previously we reported that as AKR.H-2b:Fv-1b mice become older than 9 wk of age they begin to specifically lose the ability to generate anti-AKR/Gross murine leukemia virus (MuLV) CTL responses after immunization and in vitro restimulation with cells expressing AKR/Gross MuLV-encoded Ag. Interestingly, the frequency of virus-specific precursor cytotoxic T lymphocytes (CTL) observed in moderately-aged AKR.H-2b:Fv-1b mice was not substantially decreased from that found in their young responder counterparts. To further investigate the mechanism(s) responsible for the inability of moderately-aged AKR.H-2b:Fv-1b mice to mount AKR/Gross MuLV-specific CTL responses, adoptive transfer experiments were performed in the present study. Transferring splenocytes from moderately-aged AKR.H-2b:Fv-1b donors into young AKR.H-2b:Fv-1b recipients resulted in inhibition of AKR/Gross MuLV-specific CTL responsiveness. Anti-Thy-1.1 plus complement depletion of T cells from the donor cell population before adoptive transfer resulted in a near complete restoration of AKR/Gross MuLV responsiveness of young recipient AKR.H-2b:Fv-1b mice suggesting that the inhibition observed in moderately aged mice was mediated by T lymphocytes. Additional experiments using depletion of T subsets before cell transfer demonstrated that inhibition of AKR/Gross MuLV-specific CTL responsiveness was mediated by a CD4-CD8+ T lymphocyte.
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03756.
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Fujii
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D000406:AKR murine leukemia virus; D000375:Aging / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007518:Isoantibodies / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D007518:Isoantibodies; C035678:anti-Thy antibody; D003165:Complement System Proteins