Role of CD8+ T cells in host resistance to systemic infection with Histoplasma capsulatum in mice.
Histoplasma capsulatum is a facultative intracellular fungus that spreads lymphohematogenously to involve organ systems rich in mononuclear phagocytes. We explored herein the in vivo effect of anti-CD8 rat mAb on the course of murine disseminated histoplasmosis. Treatment with anti-CD8 mAb caused a selective depletion of CD8+ T cells in naive mice infected with H. capsulatum. The loss of CD8+ T cells was associated with an increased number of H. capsulatum CFU in spleens and livers of mice during the first 3 wk of infection. Transgenic beta 2-microglobulin-deficient mice (beta 2 M-/-) that lack MHC class I Ag and CD8+ T cells or heterozygous littermates were injected with H. capsulatum. At wk 1 of infection, the number of CFU in livers and spleens of beta 2 M-/- mice was similar to that of littermates. At wk 2 and 3, however, the fungal burden in spleens and livers of beta 2 M-/- mice was larger than that of heterozygous littermates. H. capsulatum-immunized mice given anti-CD8 mAb manifested impaired clearance of H. capsulatum upon rechallenge with a large inoculum of yeasts when compared to immunized controls. Histopathologically, the inflammatory response in spleens and livers of CD8+ T cell-depleted mice was similar to that of mice given control Ab. The results indicate that CD8+ T cells are necessary for optimal clearance of the fungus from tissues of mice infected with H. capsulatum.
Deepe
G S
GS
Department of Medicine, University of Cincinnati College of Medicine, OH 45267-0560.
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D006658:Histoplasma / Q000276:immunology; D006660:Histoplasmosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens