HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques
| Autor: | Jean-Philippe Herbeuval, Jan Andersson, Jakob Nilsson, Genoveffa Franchini, Valentina Cecchinato, Andrew W. Hardy, Adriano Boasso, Gene M. Shearer, Monica Vaccari, Valerio W. Valeri |
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| Rok vydání: | 2008 |
| Předmět: |
Fas Ligand Protein
Anti-HIV Agents Lymphoid Tissue Immunology Palatine Tonsil Simian Acquired Immunodeficiency Syndrome HIV Infections medicine.disease_cause Fas ligand Article TNF-Related Apoptosis-Inducing Ligand Immune system Antiretroviral Therapy Highly Active medicine Immunology and Allergy Animals Humans RNA Messenger Immunodeficiency biology virus diseases Receptors Death Domain Simian immunodeficiency virus medicine.disease biology.organism_classification Virology Infectious Diseases Lymphatic system Cross-Sectional Studies Gene Expression Regulation Apoptosis Lentivirus Macaca Lymph Lymph Nodes |
| Zdroj: | AIDS |
| ISSN: | 1473-5571 |
| Popis: | Objective: To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissuesofHIV-infectedpatientsandsimianimmunodeficiencyvirus-infectedmacaques. Methods: We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV-uninfected (HIV negative) donors in a crosssectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virusinfected macaques before and after ART. Results: Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4 þ T cells from a group of HIV-positive patients as compared with that from both HIVnegative donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with HIV-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals. Conclusion: These findings suggest that HAART or ART is ineffective in reducing the expressionofapoptoticdeathreceptorsinlymphoidtissue.However,analysislimitedto blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4 þ T cells in lymphoid tissue. |
| Databáze: | OpenAIRE |
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