| First Author | Montagnoli C | Year | 2002 |
| Journal | J Immunol | Volume | 169 |
| Issue | 11 | Pages | 6298-308 |
| PubMed ID | 12444136 | Mgi Jnum | J:118777 |
| Mgi Id | MGI:3700354 | Doi | 10.4049/jimmunol.169.11.6298 |
| Citation | Montagnoli C, et al. (2002) B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans. J Immunol 169(11):6298-308 |
| abstractText | 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. |
