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Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-1 development.

C A Wenner, M L Güler, S E Macatonia, A O'Garra and K M Murphy
J Immunol February 15, 1996, 156 (4) 1442-1447;
C A Wenner
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M L Güler
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S E Macatonia
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A O'Garra
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K M Murphy
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Abstract

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.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 156, Issue 4
15 Feb 1996
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Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-1 development.
C A Wenner, M L Güler, S E Macatonia, A O'Garra, K M Murphy
The Journal of Immunology February 15, 1996, 156 (4) 1442-1447;

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Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-1 development.
C A Wenner, M L Güler, S E Macatonia, A O'Garra, K M Murphy
The Journal of Immunology February 15, 1996, 156 (4) 1442-1447;
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Print ISSN 0022-1767        Online ISSN 1550-6606