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1996-02-27
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Document 0530
DOCN M9630530
TI Altered cytokine expression in T lymphocytes from human immunodeficiency
virus Tat transgenic mice.
DT 9603
AU Brady HJ; Abraham DJ; Pennington DJ; Miles CG; Jenkins S; Dzierzak EA;
Laboratory of Gene Structure and Expression, National Institute; for
Medical Research, Mill Hill, London, United Kingdom.
SO J Virol. 1995 Dec;69(12):7622-9. Unique Identifier : AIDSLINE
MED/96079007
AB Examination of the interaction between human immunodeficiency virus
(HIV) regulatory gene products and the host immune system is fundamental
to understanding the pathogenesis of HIV and could reveal possible
targets for therapeutic intervention in the treatment of AIDS. The HIV
Tat gene is a potential candidate for this type of strategy. Transgenic
mice can be used to investigate the in vivo effects of Tat on the
developing and dynamic immune system and on cellular gene expression.
Thus, we have generated transgenic mice that harbor the HIV type 1 Tat
gene under the transcriptional control of the human CD2 gene regulatory
elements. This expression cassette results in high-level,
tissue-specific transcription of the transgene within the T-cell
compartment. In this report, we demonstrate the effects of Tat on the in
vivo immune system. CD2-Tat transgenic mice show no signs of aberrant
thymic development and have normal levels of T-cell subsets in the
thymus and peripheral lymphoid organs. However, activated T cells from
transgenic mice contain increased levels of tumor necrosis factor beta
mRNA as well as biologically active tumor necrosis factor protein and
express elevated levels of transforming growth factor beta and
interleukin-4 receptor mRNA. These increased cytokine levels do not
appear to alter mitogen- or antigen-stimulated responses or induce the
formation of dermal lesions in ageing mice. Such investigations should
provide insight into the combination of host immune factors mediating
pathogenesis in HIV infection.
DE Aging/IMMUNOLOGY Animal Antigens, CD/BIOSYNTHESIS Comparative Study
Cytokines/*BIOSYNTHESIS Exons Flow Cytometry Gene Expression Gene
Products, tat/ANALYSIS/*BIOSYNTHESIS *Genes, tat Human
HIV-1/*GENETICS Lymph Nodes/IMMUNOLOGY
Lymphotoxin/ANALYSIS/*BIOSYNTHESIS Mice Mice, Transgenic Receptors,
Interleukin/BIOSYNTHESIS Restriction Mapping RNA,
Messenger/ANALYSIS/BIOSYNTHESIS Spleen/IMMUNOLOGY Support, Non-U.S.
Gov't T-Lymphocytes/*MICROBIOLOGY/VIROLOGY Thymus Gland/IMMUNOLOGY
Transcription, Genetic Transforming Growth Factor beta/BIOSYNTHESIS
Tumor Necrosis Factor/BIOSYNTHESIS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).