Document 0139
 DOCN  M9650139
 TI    Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-1
       development.
 DT    9605
 AU    Wenner CA; Guler ML; Macatonia SE; O'Garra A; Murphy KM; Department of
       Pathology, Washington University School of; Medicine, St. Louis, MO
       63110, USA.
 SO    J Immunol. 1996 Feb 15;156(4):1442-7. Unique Identifier : AIDSLINE
       MED/96164572
 AB    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.
 DE    Animal  Female  Interferon Type II/*PHYSIOLOGY
       Interferon-alpha/*PHYSIOLOGY  Interleukin-12/*PHYSIOLOGY
       L-Selectin/ANALYSIS  Mice  Mice, Inbred BALB C  Receptors,
       Interleukin/METABOLISM  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  T-Lymphocyte Subsets/IMMUNOLOGY  Th1 Cells/*IMMUNOLOGY  JOURNAL
       ARTICLE

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