HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF CD4(-CELLS DOWN-REGULATES THE EXPRESSION OF CD28 - EFFECT ON T-CELL ACTIVATION AND CYTOKINE PRODUCTION() T)
Ok. Haffar et al., HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF CD4(-CELLS DOWN-REGULATES THE EXPRESSION OF CD28 - EFFECT ON T-CELL ACTIVATION AND CYTOKINE PRODUCTION() T), Clinical immunology and immunopathology, 77(3), 1995, pp. 262-270
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 alloant
igen 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 paralle
l. Virus was inducible from the infected lines with stimulation, and c
omplete infection was achieved after 4-7 weeks depending on the line.
The downmodulation of CD28 expression correlated with virus replicatio
n and spread. Furthermore, CD28 mRNA was not inducible in the infected
lines after stimulation with alloantigen. Loss of CD28 correlated wit
h reduced responsiveness to costimulation with a monoclonal antibody t
o CD28 following similar engagement of the CD3 protein. In contrast, a
ctivation with alloantigen was not affected. HIV-1 infection and down-
modulation of CD28 did not alter the relative levels of IL-2, IFN-gamm
a, and IL-4 mRNA. Production of the various cytokine mRNAs following a
lloantigen stimulation was inhibited by CTLA4Ig and thus remained unde
r the regulation oft CD80 and CD86 expressed on the EBV LCL. Taken tog
ether, our data suggest that dysregulation of normal T cell function a
ssociated with HIV-1 infection may result in part from the loss of CD2
8 expression. (C) 1995 Academic Press, Inc.