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1996-02-26
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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).