A shift in the requirement for CD4+ T cells in the generation of AKR/Gross MuLV-specific CTL in AKR.H-2b:Fv-1b mice occurs prior to the onset of age-dependent CTL nonresponsiveness.
In the current study, the elimination of CD4+ T cells from B6 mice, by treatment with anti-CD4 monoclonal antibody, had little effect on their ability to mount an AKR/Gross (MuLV)-specific CTL response. In contrast, for AKR.H-2b:Fv-1b mice, there was a shift as the mice aged from 5 to 7 weeks to a requirement for CD4+ T cells for AKR/Gross MuLV-specific CTL generation. When CD4+ T-cell-depleted AKR.H-2b:Fv-1b responder mice were immunized at 5 weeks of age they were able to elicit a strong anti-AKR/Gross MuLV CTL response. However, if the CD4+ T-cell depletion was done at 6 weeks and then the mice were primed in vivo, their antiviral CTL responsiveness was markedly decreased. Following CD4+ T-cell depletion at 7 weeks the mice were totally incapable of generating anti-AKR/Gross MuLV-specific CTL. AKR/Gross MuLV-specific CTL isolated from AKR.H-2b:Fv-1b mice recognized the class I-restricted immunodominant epitope (KSPWFTTL) and three subdominant epitopes, previously identified as CTL epitopes for B6 mice. Analysis of IL-2, IFN-gamma, IL-4, and IL-10 lymphokine profiles in supernates harvested from MLTC wells, and the results of supernate transfer experiments, suggested that the age-dependent shift to CD4+ T-cell dependence in AKR.H-2b:Fv-1b mice does not correlate with an obvious change in the in vitro lymphokine profiles. Experiments in which exogenous IL-2 was used to supplement in vitro cultures containing CD4+ T-cell-depleted 7-week responder mice suggested that the CD4+ T-cell requirement was at the in vivo priming stage of antiviral CTL generation. These data suggested a fundamental change in virus-specific CTL which correlates with slight aging in the AKR.H-2b:Fv-1b mouse strain. To our knowledge, this is the first report of a shift in the requirement for CD4+ T lymphocytes for the generation of virus-specific CTL over such a short period of time. Moreover, it is of interest that this shift in CD4+ T-cell-dependence by antiviral CTL occurs just prior to the onset of CTL nonresponsiveness in the AKR.H-2b:Fv-1b mouse strain.
Smith
P M
PM
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
Rich
R F
RF
Green
W R
WR
D000406:AKR murine leukemia virus / Q000276:immunology*; D000375:Aging / Q000276:immunology; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005622:Friend murine leukemia virus; D006183:H-2 Antigens / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007113:Immunity, Innate / Q000235:genetics; D016056:Immunodominant Epitopes / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D016056:Immunodominant Epitopes