G. Herbein et al., APOPTOSIS OF CD8(-CELLS IS MEDIATED BY MACROPHAGES THROUGH INTERACTION OF HIV GP120 WITH CHEMOKINE RECEPTOR CXCR4() T), Nature, 395(6698), 1998, pp. 189-194
CD8-positive T cells are thought to play an important role in the cont
rol of infection by human immunodeficiency virus (HIV) as a result of
their cytotoxic activity and by releasing soluble factors(1,2) in AIDS
patients, the absolute number bf CD8(+) T lymphocytes is decreased in
peripheral blood(3,4) and their turnover rate Is increased, suggestin
g that there is more cell renewal and cell death occurring(5). Anti-re
troviral therapy raises CD8(+) T-cell counts in HIV-infected patients(
6-8). Here we report that the death rate of CD8(+) T cells by apoptosi
s increased markedly during HIV infection of peripheral blood mononucl
ear cells in vitro. Apoptosis is induced in a dose-dependent manner by
recombinant envelope glycoprotein gp120 from HIV strain X4, or by str
omal-derived factor-1 (SDF-1), the physiological ligand of the chemoki
ne receptor CXCR4. Apoptosis is mediated by the interaction between tu
mour-necrosis factor-alpha bound to the membrane of macrophages (mbTNF
) and a receptor on CD8(+) T cells (TNF-receptor II, or TNFRII). The e
xpression of both of these cell surface proteins is upregulated by HIV
infection or by treatment with recombinant gp120 or SDF-1. Apoptosis
of CD8(+) T cells isolated from HIV-infected patients is also mediated
by macrophages through the interaction between mbTNF and TNFRII. Thes
e results indicate that the increased turnover of CD8(+) T cells in HI
V-infected subjects is mediated by the HIV envelope protein through th
e CXCR4 chemokine receptor.