Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells.
The role and interdependence of CD8+ and CD4+ alpha beta-T cells in the acute response after respiratory infection with the murine parainfluenza type 1 virus, Sendai virus, has been analyzed for H-2b mice. Enrichment of CD8+ virus-specific CTL effectors in the lungs of immunologically intact C57BL/6 animals coincided with the clearance of the virus from this site by day 10 after infection. Removal of the CD4+ T cells by in vivo mAb treatment did not affect appreciably either the recruitment of CD8+ T cells to the infected lung, or their development into virus-specific cytotoxic effectors. In contrast, depletion of the CD8+ subset delayed virus clearance, although most mice survived the infection. Transgenic H-2b F3 mice homozygous (-/-) for a beta 2 microglobulin (beta 2-m) gene disruption, which lack both class I MHC glycoproteins and mature CD8+ alpha beta-T cells, showed a comparable, delayed clearance of Sendai virus from the lung. Virus-specific, class II MHC-restricted CTL were demonstrated in both freshly isolated bronchoalveolar lavage populations and cultured lymph node and spleen tissue from the beta 2-m (-/-) transgenics. Treatment of the beta 2-m (-/-) mice with the mAb to CD4 led to delayed virus clearance and death, which was also the case for normal mice that were depleted simultaneously of the CD4+ and CD8+ subsets. These results indicate that, although classical class I MHC-restricted CD8+ cytotoxic T cells normally play a dominant role in the recovery of mice acutely infected with Sendai virus, alternative mechanisms involving CD4+ T cells exist and can compensate, in time, for the loss of CD8+ T cell function.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
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Hou
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Doherty
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Zijlstra
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Jaenisch
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JM
Katz
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007111:Immunity, Cellular; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010222:Parainfluenza Virus 1, Human / Q000254:growth & development / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I