Romani L, Mocci S, Cenci E, Mencacci A, Sbaraglia G, Puccetti P, Bistoni F
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Eur J Epidemiol. 1992 May;8(3):368-76. doi: 10.1007/BF00158570.
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.
免疫L3T4 +和Lyt-2 +淋巴细胞在小鼠获得性抗毒力白色念珠菌攻击中起重要作用，并在体外对酵母细胞产生反应时释放巨噬细胞激活细胞因子。为了确定真菌感染期间是否产生抗原（Ag）特异性细胞毒性T淋巴细胞，将来自免疫小鼠的纯化L3T4 +和Lyt-2 +淋巴细胞在同基因辅助细胞、念珠菌Ag和IL-2存在下培养。在标准的51Cr释放试验中，将酵母感染的骨髓巨噬细胞和腹腔渗出液中性粒细胞用作靶细胞。培养5 - 10天后，免疫Lyt-2 +细胞对感染巨噬细胞的Ag特异性、MHC非限制性裂解明显。在相同实验条件下，L3T4 +细胞的细胞毒性活性可忽略不计，但其表达可通过添加抗CD3抗体诱导。较短时间（1 - 2天）培养免疫Lyt-2 +细胞导致对感染中性粒细胞的优先裂解。此外，在效应细胞数量有限时，可鉴定出对感染巨噬细胞具有细胞毒性活性的Ag特异性MHC限制性淋巴细胞。我们认为白色念珠菌感染刺激了多种具有不同识别严格度的细胞毒性T细胞前体，这可能在体内抗真菌抗性中起重要作用。
