Moser S A, Domer J E
Infect Immun. 1980 Feb;27(2):376-86. doi: 10.1128/iai.27.2.376-386.1980.
Male CBA/J mice were given a single dose of 200 mg of cyclophosphamide (CY) per kg 3 days before a first or second cutaneous inoculation with viable Candida albicans in an attempt to suppress antibody formation and determine the effects of such suppression on the development of acquired immunity. After cutaneous inoculation, mice not treated with CY developed acquired immunity to intravenous challenge, which was accompanied by the development of circulating antibodies, delayed hypersensitivity, and in vitro responsiveness of lymph node cells to Candida antigens. CY treatment resulted in an immediate depression of peripheral blood leukocytes, with polymorphonuclear leukocytes and monocytes rebounding quickly to normal or above normal levels while lymphocyte remained depressed throughout the 4-week observation period. In vitro stimulation of lymph node cells from CY-treated mice was depressed shortly after treatment; however, responses to phytohemagglutinin and three Candida antigens (a cell wall preparation, a membrane preparation, and soluble cytoplasmic substances) recovered, whereas the responses to lipopolysaccharide did not. CY effects on the cutaneous lesion were twofold; first, the number of viable Candida cells in the lesions was much higher in animals receiving CY 3 days before Candida inoculation, and second, the size of the dermal lesion was either greatly enhanced or reduced depending upon the time of CY treatment relative to the number of cutaneous Candida inoculations. CY-treated animals developed higher levels of delayed hypersensitivity to the membrane preparation when infected once cutaneously than did corresponding untreated animals. The number of mice responding with circulating antibodies to soluble cytoplasmic substances after cutaneous inoculation was greatly reduced in CY-treated groups, and this impaired ability to produce antibodies correlated with the poor survival of these mice after intravenous challenge. Our results suggest that the ability to produce antibody at the time of challenge is crucial to successful defense against systemic candidiasis in this murine model.
在首次或第二次皮肤接种活白色念珠菌前3天，给雄性CBA/J小鼠每千克体重单次注射200毫克环磷酰胺（CY），以抑制抗体形成，并确定这种抑制对获得性免疫发展的影响。皮肤接种后，未接受CY治疗的小鼠对静脉内攻击产生了获得性免疫，同时伴有循环抗体的产生、迟发型超敏反应以及淋巴结细胞对念珠菌抗原的体外反应性。CY治疗导致外周血白细胞立即减少，多形核白细胞和单核细胞迅速反弹至正常或高于正常水平，而淋巴细胞在整个4周观察期内一直处于减少状态。治疗后不久，CY处理小鼠的淋巴结细胞体外刺激受到抑制；然而，对植物血凝素和三种念珠菌抗原（细胞壁制剂、膜制剂和可溶性细胞质物质）的反应恢复了，而对脂多糖的反应未恢复。CY对皮肤病变有双重影响；第一，在念珠菌接种前3天接受CY的动物病变中活念珠菌细胞数量要高得多；第二，皮肤病变的大小要么大大增加，要么减小，这取决于CY治疗时间与皮肤念珠菌接种次数的关系。与相应的未处理动物相比，经CY处理的动物经皮肤感染一次后对膜制剂产生的迟发型超敏反应水平更高。CY处理组中，皮肤接种后产生循环抗体以应对可溶性细胞质物质的小鼠数量大大减少，而这种产生抗体能力的受损与这些小鼠静脉内攻击后的低存活率相关。我们的结果表明，在攻击时产生抗体的能力对于在该小鼠模型中成功抵御系统性念珠菌病至关重要。
