       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).

