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 CD95 high 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.
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 CD95 high 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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