COSTIMULATION OF T-CELL ACTIVATION AND VIRUS PRODUCTION BY B7-ANTIGENON ACTIVATED CD4-CELLS FROM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED DONORS( T)
Ok. Haffar et al., COSTIMULATION OF T-CELL ACTIVATION AND VIRUS PRODUCTION BY B7-ANTIGENON ACTIVATED CD4-CELLS FROM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED DONORS( T), Proceedings of the National Academy of Sciences of the United Statesof America, 90(23), 1993, pp. 11094-11098
Infection with the human immunodeficiency virus type 1 (HIV-1) require
s T-cell activation. Recent studies have shown that interactions of th
e T-lymphocyte receptors CD28 and CTLA-4 with their counter receptor,
B7, on antigen-presenting cells are required for optimal T-cell activa
tion. Here we show that HIV-1 infection is associated with decreased e
xpression of CD28 and increased expression of B7 on CD4+ T-cell lines
generated from seropositive donors by alloantigen stimulation. Loss of
CD28 expression was not seen on CD4+ T-cell lines from seronegative d
onors, but up-regulation of B7 expression was observed upon more prolo
nged culture. Both T-cell proliferation and interleukin 2 mRNA accumul
ation in HIV-1-infected cultures required costimulation with exogenous
B7 because these events were blocked by CTLA4Ig, a soluble form of CT
LA-4 that binds B7 with high avidity. In contrast, levels of HIV-1 RNA
were not affected by CTLA4Ig, indicating that regulation of virus tra
nscription in these cultures did not depend upon CD28-B7 engagement. I
nfected T cells could present alloantigen to fresh, uninfected CD4+ T
cells, leading to increased proliferation and virus spread to the acti
vated cells. Both of these events were blocked by CTLA4Ig. Thus, chron
ic activation of HIV-1-infected CD4+ T cells reduces expression of CD2
8 and increases expression of B7, thereby enabling these T cells to be
come antigen-presenting cells for uninfected CD4+ T cells; this might
be another mechanism for HIV-1 transmission via T-cell-T-cell contact.