Yan-Mei Jiao1, Cui-E Liu1, Li-Jing Luo1, Wei-Jun Zhu2, Tong Zhang1, Li-Guo Zhang3, Li-Shan Su4, Hong-Jun Li5, Hao Wu6. 1. Beijing You'an Hospital, Capital Medical University, Beijing 100069, China. 2. MOH Key Laboratory of Systems Biology of Pathogens and AIDS Research Center, Institute of Pathogen Biology, Beijing, China. 3. Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. 4. Lineberger Comprehensive Cancer Center, UNC School of Medicine, NC, USA. 5. Beijing You'an Hospital, Capital Medical University, Beijing 100069, China. Electronic address: lihongjun00113@126.com. 6. Beijing You'an Hospital, Capital Medical University, Beijing 100069, China. Electronic address: whdoc900@gmail.com.
Abstract
BACKGROUND: A major question when attempting to eradicate and treat HIV-1 infection is how to reactivate latent proviruses. Stimulating HIV-1-specific cytolytic T lymphocytes (CTL) has been shown to facilitate the elimination of the latent viral reservoir after viral reactivation. Regulatory T (Treg) cells are known to be capable of lowering both HIV-specific immunoreactions and general immune activation during HIV-1 infection. It was hypothesized that the depletion of Treg cells could increase the HIV-1-specific cytolytic T lymphocyte response and reactivate HIV-1 p24 production. METHODS: Treg cells were isolated by isolation kit according to the surface marker of Treg cells. Real-time PCR method was used to quantify HIV-1 DNA. P24 antigens in the cell culture supernatant was done by ELISA. Cells activation and HIV specific HIV-1 CD8+ T cells were analyses using a FACSCalibur flow cytometer and CELLQUEST software. RESULTS: This study included both HIV-infected patients who were antiviral treatment-naïve and patients with sustained viral responses to antiretroviral therapy (ART) for 1 or 5 years. It was found that the HIV-DNA levels in Treg cells were approximately 10-fold higher than those in non-Treg CD4+ cells and that the depletion of Treg cells could enhance the frequency of HIV-1-specific CTL and immune activation after 5 years of effective ART. CONCLUSIONS: CD4+CD25+CD127 regulatory cells play multiple roles in maintaining HIV-1 p24 production in long-term ART patients. Treg cells may be a target for eliminating the latent HIV reservoir after effective long-term ART.
BACKGROUND: A major question when attempting to eradicate and treat HIV-1 infection is how to reactivate latent proviruses. Stimulating HIV-1-specific cytolytic T lymphocytes (CTL) has been shown to facilitate the elimination of the latent viral reservoir after viral reactivation. Regulatory T (Treg) cells are known to be capable of lowering both HIV-specific immunoreactions and general immune activation during HIV-1 infection. It was hypothesized that the depletion of Treg cells could increase the HIV-1-specific cytolytic T lymphocyte response and reactivate HIV-1p24 production. METHODS: Treg cells were isolated by isolation kit according to the surface marker of Treg cells. Real-time PCR method was used to quantify HIV-1 DNA. P24 antigens in the cell culture supernatant was done by ELISA. Cells activation and HIV specific HIV-1 CD8+ T cells were analyses using a FACSCalibur flow cytometer and CELLQUEST software. RESULTS: This study included both HIV-infectedpatients who were antiviral treatment-naïve and patients with sustained viral responses to antiretroviral therapy (ART) for 1 or 5 years. It was found that the HIV-DNA levels in Treg cells were approximately 10-fold higher than those in non-Treg CD4+ cells and that the depletion of Treg cells could enhance the frequency of HIV-1-specific CTL and immune activation after 5 years of effective ART. CONCLUSIONS: CD4+CD25+CD127 regulatory cells play multiple roles in maintaining HIV-1p24 production in long-term ART patients. Treg cells may be a target for eliminating the latent HIV reservoir after effective long-term ART.
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