BACKGROUND: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers. METHODS: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses. RESULTS: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control. CONCLUSIONS: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.
BACKGROUND: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers. METHODS: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses. RESULTS: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control. CONCLUSIONS: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.
Authors: Laura Pattacini; Jared M Baeten; Katherine K Thomas; Tayler R Fluharty; Pamela M Murnane; Deborah Donnell; Elizabeth Bukusi; Allan Ronald; Nelly Mugo; Jairam R Lingappa; Connie Celum; M Juliana McElrath; Jennifer M Lund Journal: J Acquir Immune Defic Syndr Date: 2016-06-01 Impact factor: 3.731
Authors: Didiana Jaramillo-Ruiz; Francisco Javier De La Mata; Rafael Gómez; Rafael Correa-Rocha; M Ángeles Muñoz-Fernández Journal: PLoS One Date: 2016-01-19 Impact factor: 3.240
Authors: Timothy Q Crawford; Fredrick M Hecht; Christopher D Pilcher; Lishomwa C Ndhlovu; Jason D Barbour Journal: PLoS One Date: 2013-10-15 Impact factor: 3.240