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1996-02-26
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).