Analysis of role of CD8+ T cells in resistance to murine AIDS in A/J mice.
The mixture of retroviruses termed LP-BM5 murine leukemia virus (MuLV) contains a replication-defective genome (BM5def), the crucial element for induction of murine AIDS (MAIDS), as well as helper B-tropic ecotropic and mink cell focus-forming MuLV. Among Fv-1b mouse strains, C57BL mice are sensitive to infection by these viruses and to development of MAIDS, but A/J mice are highly resistant to all viral components and to induction of disease. Inasmuch as previous genetic studies indicated a major role in susceptibility for the H-2D locus within the MHC, the effect of CD8+ T cells in A/J resistance to MAIDS was analyzed by depletion of this subset using mAb. A/J mice treated with anti-CD8 mAb beginning soon after inoculation with LP-BM5 MuLV developed disease within 5 wk after virus inoculation. Histopathologic and flow cytometry alteration of tissues and cells from the mAb-treated mice were identical to those seen in virus-infected MAIDS-sensitive strains, and assays for MuLV demonstrated high-level expression of ecotropic MuLV and integration of BM5def. Parallel studies of A/J mice treated with anti-CD4 mAb after infection revealed enhanced expression of ecotropic MuLV but no integration of BM5def, and no signs of MAIDS were detected. These observations indicate that CD8+ T cells are critical in the resistance of A/J mice to LP-BM5 MuLV replication and development of disease and suggest that CD4+ T cells play a role in regulation of ecotropic virus replication.
Makino
M
M
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Chattopadhyay
S K
SK
Hartley
J W
JW
Morse
H C
HC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology; D016827:CD8 Antigens / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D007371:Interferon-gamma