Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-1 development
| Autor: | C A Wenner, M L Güler, S E Macatonia, A O'Garra, K M Murphy |
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| Rok vydání: | 1996 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 156:1442-1447 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.156.4.1442 |
| Popis: | IL-12 and IL-4 direct T cell development toward Th1 and Th2 phenotypes, respectively. While IFN-gamma and IFN-alpha have been reported to regulate Th1 development as well, the mechanism and cellular locus of their effects are unclear. In this study, we use a TCR-transgenic system to examine the actions of these cytokines on CD4+ T cell phenotype development. We find that neither IFN-gamma nor IFN-alpha can induce Th1 development alone. However, IFN-gamma can significantly augment IL-12 priming for subsequent IFN-gamma production by T cells. Interestingly, lymphocyte endothelial cell adhesion molecule-1bright (naive) T cells require IFN-gamma during primary activation for maximal IL-12-induced Th1 development, whereas lymphocyte endothelial cell adhesion molecule-1dull (memory) T cells do not. IFN-alpha only partially substitutes for IFN-gamma in promoting IL-12-induced Th1 development. When the endogenous IFN-gamma present in primary T cell cultures is neutralized, IFN-alpha treatment augments IL-12-induced effects on inhibition of subsequent IL-4 production, but fails to significantly enhance IL-12 priming for subsequent IFN-gamma production. Thus, our data suggest that IFN-gamma provides a direct costimulatory signal to T cells to up-regulate IL-12-induced Th1 development and may operate by inducing IL-12 responsiveness in naive T cells. |
| Databáze: | OpenAIRE |
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