First Author | Wüthrich M | Year | 2005 |
Journal | J Immunol | Volume | 175 |
Issue | 8 | Pages | 5288-97 |
PubMed ID | 16210634 | Mgi Jnum | J:119110 |
Mgi Id | MGI:3701182 | Doi | 10.4049/jimmunol.175.8.5288 |
Citation | Wuthrich M, et al. (2005) IL-12 is required for induction but not maintenance of protective, memory responses to Blastomyces dermatitidis: implications for vaccine development in immune-deficient hosts. J Immunol 175(8):5288-97 |
abstractText | Cellular immunity mediated by T lymphocytes, in particular CD4(+) and CD8(+) type 1 (T1) cells, is the main defense against pathogenic fungi. IL-12 initiates T1 cell development and cell-mediated immunity, but it is unclear whether IL-12 contributes to the maintenance of an antifungal T1 response. In this study, we addressed the role of IL-12 for vaccine-induced memory T cell development against experimental pulmonary blastomycosis. CD4(+) T cells absolutely required IL-12 to control a live genetically engineered attenuated strain of Blastomyces dermatitidis given s.c. as a vaccine, whereas CD8(+) T cells were significantly less dependent on IL-12. Despite differential dependency of T cell subsets on IL-12 during vaccination, neither subset acquired memory immunity in the absence of IL-12. In contrast, adoptive transfer of immune CD4 T cells from wild-type mice into IL-12(-/-) mice showed that CD4(+) T1 memory cells sustained a T1 cytokine profile and remained protective over a period of 6 mo posttransfer. Similarly, memory CD8 cells elicited in IL-12(-/-) mice with killed yeast and transient rIL-12 treatment (during vaccination) remained durable and protective after animals were rested for 3 mo. In conclusion, these studies demonstrate that once CD4 and CD8 cells have acquired a protective T1 phenotype they no longer require the presence of IL-12 to maintain antifungal protective memory. |