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J. Virol., Aug 1996, 4953-4960, Vol 70, No. 8
D Schols and E De Clercq
The effects of recombinant gp120 on the proliferative responses and
cytokine production by normal peripheral blood mononuclear cells (PBMC)
were investigated. gp120 inhibited in a dose-dependent fashion the anti-
CD3 monoclonal antibody (MAb)- and concanavalin A-induced proliferative
responses. The production of interleukin-2 (IL-2) and IL-4 was diminished
by gp120 in the anti-CD3- and concanavalin A-stimulated cultures. In
unstimulated PBMC, gp120 induced the production of considerable amounts of
IL-10, gamma interferon, and tumor necrosis factor alpha. The gp120-induced
reduction in the proliferative responses of PBMC was at least partially
reversed by the addition of IL- 2, anti-CD28 MAb, or transfectants
expressing CD80, CD86, or CD40 but not with exogenous IL-4. Also, a
neutralizing anti-IL-10 MAb reversed the inhibitory effect of gp120 on the
proliferative responses whereas exogenous IL-10 further enhanced this
inhibitory effect. These findings indicate that IL-10 plays an important
role in the inhibitory effect of gp120 on PBMC proliferation. The ratio of
CD3+CD4+ to CD3+CD8+ T cells was the same in gp120-treated and untreated
cell cultures. No apoptosis in these two T-cell populations was observed.
However, the number of activated CD3+CD4+ T cells and CD3+CD8+ T cells, as
judged by CD25, CD69, and HLA-DR expression, was consistently reduced.
gp120 induced the expression of IL-10 in the monocyte/macrophage
population, and therefore gp120 also reduced the proliferative responses of
CD4+ T-cell- depleted PBMC. Taken together, our observations point to the
importance of the cytokine pattern changes and, in particular, the role of
IL-10 (produced by the monocytes) in the inhibitory effect of gp120. This
mechanism of gp120-induced immunosuppression, if operative in vivo, could
contribute to the depressed immune responses associated with human
immunodeficiency virus infection and thus have important implications for
immunotherapeutic strategies to slow down disease progression in AIDS.
Copyright © 1996, American Society for Microbiology
Human immunodeficiency virus type 1 gp120 induces anergy in human peripheral blood lymphocytes by inducing interleukin-10 production
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
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