Fidel P L, Lynch M E, Sobel J D
Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
Infect Immun. 1993 Oct;61(10):4202-7. doi: 10.1128/iai.61.10.4202-4207.1993.
The role of systemic cell-mediated immunity (CMI) as a host defense mechanism in the vagina is poorly understood. Using a murine pseudoestrus model of experimental vaginal candidiasis, we previously found that animals given a vaginal inoculum of viable Candida albicans blastoconidia acquired a persistent vaginal infection and developed Candida-specific delayed-type hypersensitivity (DTH) responses. The present study was designed to characterize the peripheral CMI reactivity generated from the vaginal infection in mice and to determine whether pseudoestrus is a prerequisite for the induction of peripheral CMI reactivity. Mice treated or not treated with estrogen and given a vaginal inoculum of C. albicans blastoconidia were examined for 4 weeks for their vaginal Candida burden and peripheral CMI reactivity, including DTH responsiveness and in vitro Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma]/Th2 (IL-4, IL-10)-type lymphokine production in response to Candida antigens. Results showed that although mice not treated with estrogen before being given a vaginal inoculum of C. albicans blastoconidia developed only a short-lived vaginal infection and harbored significantly fewer Candida CFU in the vagina compared with those given estrogen and then infected; DTH reactivity was equivalent in both groups. In vitro measurement of CMI reactivity further showed that lymph node cells from both estrogen- and non-estrogen-treated infected mice produced elevated levels of IL-2 and IFN-gamma in response to Candida antigens during the 4 weeks after vaginal inoculation. In contrast, lymph node cells from the same vaginally infected mice showed no IL-10 production and only small elevations of IL-4 during week 4 of infection. These results suggest that mice with experimental vaginal candidiasis develop predominantly Th1-type Candida-specific peripheral CMI reactivity and that similar patterns of Th1-type reactivity occur in mice regardless of the persistence of infection and the estrogen status of the infected mice.
作为一种宿主防御机制，全身细胞介导免疫（CMI）在阴道中的作用尚不清楚。利用实验性阴道念珠菌病的小鼠假动情模型，我们之前发现，接种活白色念珠菌芽生孢子的动物会发生持续性阴道感染，并产生念珠菌特异性迟发型超敏反应（DTH）。本研究旨在表征小鼠阴道感染产生的外周CMI反应性，并确定假动情是否是诱导外周CMI反应性的先决条件。对接种白色念珠菌芽生孢子的小鼠，给予或不给予雌激素处理，观察4周，检测其阴道念珠菌负荷和外周CMI反应性，包括DTH反应性以及体外对念珠菌抗原产生的Th1（白细胞介素-2 [IL-2]、γ干扰素[IFN-γ]）/Th2（IL-4、IL-10）型细胞因子。结果显示，在接种白色念珠菌芽生孢子前未接受雌激素处理的小鼠，虽然仅发生短暂的阴道感染，且与接受雌激素处理后再感染的小鼠相比，阴道内的念珠菌CFU明显较少；但两组的DTH反应性相当。CMI反应性的体外检测进一步显示，在阴道接种后的4周内，接受雌激素处理和未接受雌激素处理的感染小鼠的淋巴结细胞对念珠菌抗原产生的IL-2和IFN-γ水平均升高。相反，来自相同阴道感染小鼠的淋巴结细胞在感染第4周时未产生IL-10，IL-4仅略有升高。这些结果表明，患有实验性阴道念珠菌病的小鼠主要产生Th1型念珠菌特异性外周CMI反应性，并且无论感染的持续时间和感染小鼠的雌激素状态如何，小鼠中都会出现类似的Th1型反应模式。
