Activation of the CD95 system increases with disease progression in human immunodeficiency virus type 1-infected children and adolescents

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Abstract

Background.

Increased apoptosis in infected as well as noninfected cells has been invoked in CD4+ T helper cell depletion during HIV-1 infection. A strong increase in the expression of CD95 (APO-1/Fas) and CD95 ligand, key regulators of apoptosis in normal T cells, has previously been described in freshly isolated T cells from HIV-1-positive children when compared with healthy age-matched controls. We also found an increase in spontaneous as well as specific CD95-mediated apoptosis in CD4+ and CD8+ T cells from these patients. However, the relationship of these findings to disease progression in children with HIV infection is not known.

Measurements and subjects.

We studied expression of CD95 and CD95 ligand as well as sensitivity towards spontaneous and anti-CD95-triggered apoptosis of T cells in 33 HIV-1-positive children and adolescents in different disease stages.

Results.

Loss of CD4+ T cells in vivo was paralleled by an increase in the percentage of CD95high T cells and an increase in anti-CD95-induced apoptosis of CD4+ T cells. CD95L mRNA was constantly up-regulated in T cells from patients in intermediate disease stages whereas patients with normal CD4 counts and patients with advanced T cell loss showed CD95 ligand-mRNA levels in or slightly above the range of normal controls.

Conclusions.

Disturbed regulation of the CD95 system may play an important role in the development of immunodeficiency during the course of HIV infection in children.

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