Excess apoptosis of mononuclear cells contributes to the depressed cytomegalovirus-specific immunity in HIV-infected patients on HAART
| Autor: | Renee Jesser, David A. Wohl, Charles L. Edelstein, Jerome Bill, Adriana Weinberg |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
HAART
CD14 T cell Cytomegalovirus HIV Infections Apoptosis Cysteine Proteinase Inhibitors Peripheral blood mononuclear cell Annexin V Annexin Immunity Antiretroviral Therapy Highly Active Virology medicine Humans Annexin A5 Caspase biology Cell growth HIV virus diseases Immune reconstitution crmA medicine.anatomical_structure Cytomegalovirus Infections Immunology Leukocytes Mononuclear Cell-mediated immunity biology.protein |
| DOI: | 10.17615/7bb0-5929 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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