First Author | Dighe AS | Year | 1995 |
Journal | Immunity | Volume | 3 |
Issue | 5 | Pages | 657-66 |
PubMed ID | 7584155 | Mgi Jnum | J:331605 |
Mgi Id | MGI:7388689 | Doi | 10.1016/1074-7613(95)90136-1 |
Citation | Dighe AS, et al. (1995) Tissue-specific targeting of cytokine unresponsiveness in transgenic mice. Immunity 3(5):657-66 |
abstractText | 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. |