Document 0720
 DOCN  M9620720
 TI    Human immunodeficiency virus type 1 infection of CD4+ T cells
       down-regulates the expression of CD28: effect on T cell activation and
       cytokine production.
 DT    9602
 AU    Haffar OK; Smithgall MD; Wong JG; Bradshaw J; Linsley PS; Bristol-Myers
       Squibb Pharmaceutical Research Institute, Seattle,; Washington 98121,
       USA.
 SO    Clin Immunol Immunopathol. 1995 Dec;77(3):262-70. Unique Identifier :
       AIDSLINE MED/96080354
 AB    Infection with human immunodeficiency virus type 1 (HIV-1) results in
       dysregulation of normal T cell function. To study the effects of HIV-1
       at the cellular level, primary T cell lines were generated by
       alloantigen stimulation of CD4+ T cells collected from peripheral blood
       of HIV-1-infected donors. Using Epstein-Barr virus-infected B
       lymphocytes (EBV-LCL) as a source of alloantigen, the T cell lines were
       expanded in vitro for 7 weeks. Uninfected T cell lines were cultured in
       parallel. Virus was inducible from the infected lines with stimulation,
       and complete infection was achieved after 4-7 weeks depending on the
       line. The down-modulation of CD28 expression correlated with virus
       replication and spread. Furthermore, CD28 mRNA was not inducible in the
       infected lines after stimulation with alloantigen. Loss of CD28
       correlated with reduced responsiveness to costimulation with a
       monoclonal antibody to CD28 following similar engagement of the CD3
       protein. In contrast, activation with alloantigen was not affected.
       HIV-1 infection and down-modulation of CD28 did not alter the relative
       levels of IL-2, IFN-gamma, and IL-4 mRNA. Production of the various
       cytokine mRNAs following alloantigen stimulation was inhibited by
       CTLA4Ig and thus remained under the regulation of CD80 and CD86
       expressed on the EBV-LCL. Taken together, our data suggest that
       dysregulation of normal T cell function associated with HIV-1 infection
       may result in part form the loss of CD28 expression.
 DE    Antigens, CD28/*BIOSYNTHESIS/GENETICS  Cell Line, Transformed
       Cytokines/*BIOSYNTHESIS  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY/METABOLISM/*VIROLOGY  Down-Regulation
       (Physiology)/*PHYSIOLOGY  Human  HIV Infections/IMMUNOLOGY
       HIV-1/*IMMUNOLOGY  Lymphocyte Transformation/IMMUNOLOGY  RNA,
       Messenger/ANALYSIS  JOURNAL ARTICLE

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