Short Communication: Enhanced CD8+ T Cell Apoptosis in HIV-Infected Adolescents with Virologic Failure on Protease Inhibitor-Based Therapy
| Autor: | Marvin Belzer, Jun Zuo, Bonnie J. Ank, Ingrid Schmid, Christina M. R. Kitchen, Paul Krogstad, Joseph A. Church |
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| Rok vydání: | 2010 |
| Předmět: |
Adolescent
Anti-HIV Agents Programmed Cell Death 1 Receptor Immunology Apoptosis HIV Infections Pathogenesis CD8-Positive T-Lymphocytes Biology Peripheral blood mononuclear cell Flow cytometry Young Adult Antigens CD Annexin Antiretroviral Therapy Highly Active Virology medicine Humans HIV Protease Inhibitor Cytotoxic T cell Treatment Failure Retrospective Studies medicine.diagnostic_test HIV Protease Inhibitors Viral Load Flow Cytometry Cross-Sectional Studies Infectious Diseases Apoptosis Regulatory Proteins Viral load CD8 |
| Zdroj: | AIDS Research and Human Retroviruses. 26:681-684 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2009.0112 |
| Popis: | In this study, we investigated the possibility of differential effects of protease inhibitor (PI)-containing (PI(+)) and PI-sparing (PI(-)) antiretroviral therapies (ART) on CD8(+) T cell apoptosis. We retrospectively analyzed both PD-1 expression and CD8(+) T cell apoptosis in a cross-sectional study of HIV-positive adolescents and young adults (mean age = 17.4 years), with perinatally or behaviorally acquired HIV infection. Fifty-one specimens of cryopreserved peripheral blood mononuclear cells (PBMCs) were analyzed using 7-color flow cytometry: 20 from patients receiving PI(+) ART, 14 from PI(-) ART, and 17 from the untreated. The results showed that percentages of PD-1(+) CD8(+) T cells were strongly correlated with plasma viral loads regardless of treatment (p = 0.0001). The percentage of PD-1(+) CD8(+) T cells was also positively associated with percentages of Annexin V(+) CD8(+) T cells (p = 0.04) in the PI(+)-treated group. The fraction of apoptotic (Annexin V(+)) CD8(+) T cells was associated with viral load in the patients receiving ART that contained one or more protease inhibitors (p = 0.029), but not in the PI(-) or untreated groups. In summary, we found a direct correlation between PD-1 expression on CD8(+) T cells and HIV levels that was not affected by types of medications used in the ART of those adolescents, suggesting that virological success is necessary for PD-1 downregulation. CD8(+) T cell apoptosis was linked to high levels of PD-1 expression and HIV viremia. However, there was a higher degree of apoptosis among viremic patients receiving PI therapy, suggesting an immunologically adverse effect of continuing PI(+) therapy after virological failure. |
| Databáze: | OpenAIRE |
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