HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy
| Autor: | Delphine Planas, Maged P. Ghali, Éric A. Cohen, Rémi Fromentin, Barbara L. Shacklett, Vikram Mehraj, Yuwei Zhang, Tomas Raul Wiche Salinas, Annie Gosselin, Nicolas Chomont, Jean-Pierre Routy, Petronela Ancuta, Vanessa Sue Wacleche |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Retinoic acid HIV Infections C-C chemokine receptor type 6 Polymerase Chain Reaction Medical and Health Sciences law.invention chemistry.chemical_compound 0302 clinical medicine Basic Science law T-Lymphocyte Subsets Receptors retinoic acid Immunology and Allergy Medicine Viral Polymerase chain reaction medicine.diagnostic_test virus diseases hemic and immune systems Cell sorting Middle Aged Biological Sciences Flow Cytometry Real-time polymerase chain reaction Blood Infectious Diseases Anti-Retroviral Agents central memory CD4+ T cells HIV/AIDS Female Th17 Infection central memory CD4(+) T cells Receptors CCR6 Adult Colon Immunology antiretroviral therapy HIV reservoirs chemical and pharmacologic phenomena Real-Time Polymerase Chain Reaction viral outgrowth assay Flow cytometry 03 medical and health sciences Young Adult Virology Humans Aged business.industry T-cell receptor Psychology and Cognitive Sciences Leukapheresis DNA 030104 developmental biology chemistry DNA Viral Virus Activation business CCR6 030215 immunology |
| Zdroj: | AIDS (London, England), vol 31, iss 1 AIDS (London, England) |
| Popis: | Objectives: The objective of this article is to investigate the contribution of colon and blood CD4+ T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. Design: Matched sigmoid biopsies and blood samples (n = 13) as well as leukapheresis (n = 20) were collected from chronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4+ T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA−), central memory (TCM; CD45RA−CCR7+), effector (TEM/TM; CD45RA−CCR7−), Th17 (CCR6+CCR4+), Th1Th17 (CCR6+CXCR3+), Th1 (CCR6−CXCR3+), and Th2 (CCR6−CCR4+). Methods: We used polychromatic flow cytometry for cell sorting, nested real-time PCR for HIV DNA quantification, ELISA and flow cytometry for HIV p24 quantification. HIV reactivation was induced by TCR triggering in the presence/absence of all-trans retinoic acid. Results: Compared with blood, the frequency of CCR6+ TM was higher in the colon. In both colon and blood compartments, CCR6+ TM were significantly enriched in HIV DNA when compared with their CCR6− counterparts (n = 13). In blood, integrated HIV DNA levels were significantly enriched in CCR6+ versus CCR6− TCM of four of five individuals and CCR6+ versus CCR6− TEM of three of five individuals. Among blood TCM, Th17 and Th1Th17 contributed the most to the pool of cells harboring integrated HIV DNA despite their reduced frequency compared with Th2, which were infected the least. HIV reactivation was induced by TCR triggering and/or retinoic acid exposure at higher levels in CCR6+ versus CCR6− TM, TCM, and TEM. Conclusion: CCR6 is a marker for colon and blood CD4+ T cells enriched for replication-competent HIV DNA. Novel eradication strategies should target HIV persistence in CCR6+CD4+ T cells from various anatomic sites. |
| Databáze: | OpenAIRE |
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