Antigen-specific cytolysis of infected cells in murine candidiasis.
Immune L3T4+ and Lyt-2+ lymphocytes play an important role in the acquired resistance of mice to challenge with virulent Candida albicans, and release macrophage-activating cytokines in response to yeast cells in vitro. To determine whether antigen (Ag)-specific cytotoxic T lymphocytes are generated during fungal infection, purified L3T4+ and Lyt-2+ lymphocytes from immunized mice were cultured in the presence of syngeneic accessory cells, Candida Ag, and IL-2. Yeast-infected bone marrow macrophages and peritoneal exudate neutrophils were used as target cells in a standard 51Cr release assay. Ag-specific, MHC-unrestricted lysis of infected macrophages was evident with immune Lyt-2+ cells after 5-10 days in culture. Under the same experimental conditions, the cytotoxic activity of L3T4+ cells was negligible, but its expression could be induced by the addition of anti-CD3 antibody. Culturing immune Lyt-2+ cells for shorter periods of time (1-2 days) resulted in preferential lysis of infected neutrophils. In addition, at limiting effector cell numbers, Ag-specific MHC-restricted lymphocytes with cytotoxic activity to infected macrophages could be identified. We suggest that C. albicans infection stimulates multiple cytotoxic T-cell precursors with varying recognition stringency, which may have an important role in antifungal resistance in vivo.
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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L
Romani
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Mocci
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E
Cenci
A
A
Mencacci
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Sbaraglia
P
P
Puccetti
F
F
Bistoni
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000946:Antigens, Fungal / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002177:Candidiasis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007376:Interleukin-2 / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000946:Antigens, Fungal; D000950:Antigens, Ly; D007376:Interleukin-2