Document 0812
 DOCN  M9620812
 TI    Tissue-specific targeting of cytokine unresponsiveness in transgenic
       mice.
 DT    9602
 AU    Dighe AS; Campbell D; Hsieh CS; Clarke S; Greaves DR; Gordon S; Murphy
       KM; Schreiber RD; Center for Immunology, Washington University School of
       Medicine,; St. Louis, Missouri 63110, USA.
 SO    Immunity. 1995 Nov;3(5):657-66. Unique Identifier : AIDSLINE
       MED/96074241
 AB    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.
 DE    Animal  B-Lymphocytes/DRUG EFFECTS  Cell Differentiation/DRUG EFFECTS
       Female  Human  Interferon Type II/*PHARMACOLOGY
       Interleukin-12/BIOSYNTHESIS  Killer Cells, Natural/DRUG EFFECTS
       Macrophages, Peritoneal/*DRUG EFFECTS/METABOLISM  Mice  Mice, Inbred
       BALB C  Mice, Inbred C3H  Mice, Inbred C57BL  Mice, Transgenic
       Neutrophils/DRUG EFFECTS  Organ Specificity/PHYSIOLOGY  Receptors,
       Interferon/BIOSYNTHESIS/*DRUG EFFECTS  Recombinant Proteins/PHARMACOLOGY
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Th1 Cells/DRUG
       EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).