Mody C H, Tyler C L, Sitrin R G, Jackson C, Toews G B
Department of Internal Medicine, University of Calgary, Alberta, Canada.
Am J Respir Cell Mol Biol. 1991 Jul;5(1):19-26. doi: 10.1165/ajrcmb/5.1.19.
Cryptococcus neoformans is a pathogenic yeast causing disease predominantly in immunosuppressed patients. C. neoformans is acquired by the pulmonary route, where the alveolar macrophage (AM) is a resident mechanism of host defense. The ability of rat AM to be activated by products of the immune response for enhanced anticryptococcal effect has not previously been demonstrated. Rat AM could be activated in vitro for anticryptococcal activity by medium conditioned by concanavalin A-stimulated splenic lymphocytes. A monoclonal antibody that neutralizes interferon-gamma (IFN-gamma) inhibited the macrophage-activating activity of lymphokine-containing medium (LCM). Further, recombinant IFN-gamma activated AM for anticryptococcal activity. The concentration of IFN-gamma in LCM, determined by enzyme-linked immunosorbent assay, was equivalent to the range of concentrations of recombinant IFN-gamma which activated AM. Thus, IFN-gamma was necessary and sufficient for optimal macrophage activation by medium conditioned by proliferating lymphocytes. Lipopolysaccharide could not enhance the anticryptococcal activity produced by optimal concentrations of LCM or IFN-gamma but did augment the effects of submaximal stimulation. Both LCM and recombinant IFN-gamma increased the percentage of macrophages with cell-associated cryptococcus, suggesting that activation of AM enhanced the adhesion or uptake of cryptococcus. We speculate that inadequate availability of lymphokines such as IFN-gamma may result in the immunodeficient state in hosts unable to generate an appropriate response to cryptococcal antigens. Administration of lymphokines such as IFN-gamma to immunosuppressed hosts might circumvent the defect in cell-mediated immunity.
新型隐球菌是一种致病性酵母，主要在免疫抑制患者中引发疾病。新型隐球菌通过肺部途径感染，肺泡巨噬细胞（AM）是宿主防御的固有机制。此前尚未证明大鼠肺泡巨噬细胞能够被免疫反应产物激活以增强抗隐球菌作用。用伴刀豆球蛋白A刺激的脾淋巴细胞培养的条件培养基可在体外激活大鼠肺泡巨噬细胞产生抗隐球菌活性。一种中和干扰素-γ（IFN-γ）的单克隆抗体可抑制含淋巴细胞因子的培养基（LCM）的巨噬细胞激活活性。此外，重组IFN-γ可激活肺泡巨噬细胞产生抗隐球菌活性。通过酶联免疫吸附测定法测定，LCM中IFN-γ的浓度与激活肺泡巨噬细胞的重组IFN-γ浓度范围相当。因此，IFN-γ对于由增殖淋巴细胞培养的条件培养基实现最佳巨噬细胞激活是必要且充分的。脂多糖不能增强最佳浓度的LCM或IFN-γ产生的抗隐球菌活性，但可增强次最大刺激的效果。LCM和重组IFN-γ均增加了与细胞相关的隐球菌的巨噬细胞百分比，表明肺泡巨噬细胞的激活增强了隐球菌的黏附或摄取。我们推测，诸如IFN-γ等淋巴细胞因子的可用性不足可能导致宿主出现免疫缺陷状态，无法对隐球菌抗原产生适当反应。向免疫抑制宿主施用诸如IFN-γ等淋巴细胞因子可能会规避细胞介导免疫的缺陷。
