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The ubiquitous cellular distribution of certain cytokine receptors has hampered attempts to define the physiologically important cell-specific functions of cytokines in vivo. Herein, we report the generation of transgenic mice that express a dominant-negative IFN gamma receptor alpha chain mutant under the control of either the human lysozyme promoter or the murine lck proximal promoter, which display tissue-specific unresponsiveness in the macrophage or T cell compartments, respectively, to the pleiotropic cytokine, IFN gamma. We utilize these mice to identify previously undefined cellular targets of IFN gamma action in the development of a murine antimicrobial response and the mixed lymphocyte reaction. Moreover, we identify the macrophage as a critical responsive cell in manifesting the effects of IFN gamma in regulating CD4+ T helper subset development. These studies thus represent a novel approach to studying the cell-specific actions of an endogenously produced pleiotropic cytokine in vivo.

Type

Journal article

Journal

Immunity

Publication Date

11/1995

Volume

3

Pages

657 - 666

Keywords

Animals, B-Lymphocytes, Cell Differentiation, Female, Humans, Interferon-gamma, Interleukin-12, Killer Cells, Natural, Macrophages, Peritoneal, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Neutrophils, Organ Specificity, Receptors, Interferon, Recombinant Proteins, Th1 Cells