B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans
B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans
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DOI：
10.4049/jimmunol.169.11.6298
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发表时间：
2002-12-01
影响因子：
4.4
通讯作者：
Romani, L
中科院分区：
文献类型：
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作者：
Montagnoli, C;Bacci, A;Romani, L
对白色念珠菌的保护性免疫是由抗原特异性的Th1细胞介导的。矛盾的是，某些Th2细胞因子是维持Th1介导的对真菌的免疫抵抗所必需的。因此，除了Th1/Th2平衡外，似乎还有其他机制参与调节Th1对真菌的免疫。在这里，我们表明，在念珠菌病小鼠中产生了CD4(+)CD25(+)T细胞，负向调节抗真菌Th1反应。在B7-2或CD28缺陷小鼠或IL-10信号缺乏的情况下，不能产生CD4(+)CD25(+)T细胞。因此，尽管这些小鼠能够有效地限制真菌的生长，但它们经历了炎症病理，并且不能抵抗再次感染。CD4(+)CD25(+)T细胞在体外增殖不良；高度富含产生IL-4、IL-10和转化生长因子-β的细胞；需要产生IL-10的假丝酵母菌激活的树突状细胞。过继转移CD4(+)CD25(+)T细胞或产生IL-10的树突状细胞可以恢复B7-2缺陷小鼠对再感染的抵抗力并减少炎症。这些结果表明，酵母引发的持久保护性免疫需要念珠菌菌丝诱导的口服耐受性。这意味着，防止再次激活而不是支持对无处不在的真菌病原体的灭菌免疫可能代表了基于疫苗的策略的最终期望。
Protective immunity to the fungus Candida albicans is mediated by Ag-specific Th1 cells. Paradoxically, some Th2 cytokines are required for the maintenance of Th1-mediated immune resistance to the fungus. Therefore, in addition to the Th1/Th2 balance, other mechanisms seem to be involved in the regulation of Th1 immunity to the fungus. Here we show that CD4(+)CD25(+) T cells, negatively regulating antifungal Th1 reactivity, are generated in mice with candidiasis. CD4(+)CD25(+) T cells were not generated in B7-2- or CD28-deficient mice or in condition of IL-10 signaling deficiency. Accordingly, although capable of efficiently restricting the fungal growth, these mice experienced inflammatory pathology and were incapable of resistance to reinfection. CD4(+)CD25(+) T cells poorly proliferated in vitro; were highly enriched for cells producing IL-4, IL-10, and TGF-beta; and required IL-10-producing, Candida hypha-activated dendritic cells for generation. Adoptive transfer of CD4(+)CD25(+) T cells or IL-10-producing dendritic cells restored resistance to reinfection and decreased inflammation in B7-2-deficient mice. These results show that oral tolerance induced by Candida hyphae is required for the occurrence of long-lasting protective immunity after yeast priming. The implication is that preventing reactivation rather than favoring sterilizing immunity to ubiquitous fungal pathogens may represent the ultimate expectation of vaccine-based strategies.