Excess apoptosis of mononuclear cells contributes to the depressed cytomegalovirus-specific immunity in HIV-infected patients on HAART |
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Authors: | Weinberg Adriana Jesser Renee D Edelstein Charles L Bill Jerome R Wohl David A |
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Affiliation: | Department of Pediatrics of the University of Colorado Health Sciences Center, Denver, CO 80220, USA. Adriana.Weinberg@uchsc.edu |
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Abstract: | HIV-infected patients on highly active antiretroviral therapy (HAART) have persistently decreased cytomegalovirus (CMV)-specific proliferative responses [lymphocyte proliferation assay (LPA)] in spite of increases in CD4+ T cell counts. Here we demonstrate an association between apoptosis of unstimulated peripheral blood mononuclear cells (uPBMC) and decreased CMV-LPA. HAART recipients had more apoptosis of uPBMC than controls when measured by caspases 3, 8, and 9 activities and by annexin V binding. Patients with undetectable HIV replication maintained significantly higher apoptosis of CD4+ and CD14+ cells compared to controls. CMV-LPA decreased with higher apoptosis of uPBMC in patients only. This association was independent of CD4+ cell counts or HIV replication. Furthermore, rescuing PBMC from apoptosis with crmA, but not with TRAIL- or Fas-pathway blocking agents or with other caspase inhibitors, increased CMV-LPA in HAART recipients. This effect was not observed in uninfected controls, further indicating that the down regulatory effect of apoptosis on cell-mediated immunity (CMI) was specifically associated with the HIV-infected status. |
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Keywords: | Immune reconstitution Apoptosis HIV HAART Cell-mediated immunity Cytomegalovirus Caspase Annexin V crmA |
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