International Immunology, Vol 9, 1453-1462, Copyright © 1997 by Oxford University Press
M Kameoka, S Suzuki, T Kimura, K Fujinaga, W Auwanit, RB Luftig and K Ikuta
Apoptosis is a major mechanism whereby HIV-1 depletes uninfected CD4+ and
CD8+ T cells. We previously showed that resting peripheral blood T cells
derived from healthy donors were killed by an apoptotic mechanism after
adsorption to gp120-containing, protease-defective HIV-1 (L-2) particles,
more effectively than parental wild-type LAI adsorption or rgp 120-mediated
CD4 cross-linking, followed by mitogenic stimulation. Here, we present
evidence that the L-2 particle-based apoptosis was induced both in CD4+ and
CD8+ cells by generation of effector cells which were mainly derived from a
resting memory CD4+CD38- subset. This subset enhanced the CD25 expression
on the surface and secreted IFN- gamma in the culture supernatant after L-2
particle exposure. Significant elevation of Fas ligand mRNA was found in
the subset by L-2 particle exposure, while expression of Fas antigen on
uninfected T cells was induced by exposure to IFN-gamma. These results
indicate that L-2 particles can shift the CD4+CD38- subpopulation from a
resting to an activated state, and this activation leads to killing of
bystander CD4+ and CD8+ T cells by a Fas-mediated mechanism. In fact,
purified CD4+CD38- cells exposed to L-2 particles were converted into
effector cells that were able to kill autologous as well as allogenic
target T cells pretreated with IFN-gamma. Further, we found that the
observation of apoptosis due to L-2 particles was a more general
phenomenon, that also occurred with Thai primary HIV-1 isolates. These
results suggest that such specific types of HIV-1 particles may play a
major role in the induction of apoptosis for both bystander CD4+ and CD8+ T
cells, through inappropriate activation of CD4+CD38- cells.
ARTICLES
Exposure of resting peripheral blood T cells to HIV-1 particles generates CD25+ killer cells in a small subset, leading to induction of apoptosis in bystander cells
Section of Serology, Hokkaido University, Sapporo, Japan.
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