Isaac Rosado-Sánchez1, Inés Herrero-Fernández2, Laura Tarancon-Diez2, Santiago Moreno3, Jose Antonio Iribarren4, David Dalmau5, Francisco Vera-Méndez6, Manuel Leal2, Yolanda María Pacheco7. 1. Laboratory of Immunovirology, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville 41013, Spain. Electronic address: isaac_rosado@hotmail.com. 2. Laboratory of Immunovirology, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville 41013, Spain. 3. Ramón y Cajal University Hospital, Madrid 28034, Spain. 4. Donostia University Hospital, San Sebastián/Donostia 20014, Spain. 5. Mútua Terrassa University Hospital, Terrassa 08221, Spain. 6. Santa Lucía University Hospital, Cartagena 30202, Spain. 7. Laboratory of Immunovirology, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville 41013, Spain. Electronic address: ypacheco-ibis@us.es.
Abstract
BACKGROUND: Despite the fact that antiretroviral therapy (cART) suppresses HIV-viremia, an adequate CD4 T-cell recovery is not always achieved (immunodiscordant response to cART). IL17a-producing CD4 T-cells (Th17) constitutes an important subset involved in the preservation of mucosal surfaces integrity, which depletion has been associated with disease progression in HIV-infection. However, whether Th17 frequency at cART initiation is associated with a poor CD4 T-cell recovery has not been yet explored. Our aim was to explore whether the Th17 cells and other IL17a-producing T-cell subsets at cART initiation were associated with a subsequent immunodiscordant response to cART. METHODS: We selected pre-cART samples of antiretroviral-naïve subjects with and without a low CD4 recovery after cART (LR-subjects and HR-subjects, respectively). Peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/ionomycine, and the production of several cytokines including IL17a was analyzed by flow cytometry. RESULTS: A trend to higher Th17 (p = 0.05) and increased frequencies of IL17a-producing Treg (p = 0.011) was found in LR-subjects before cART onset. Despite increased frequencies of both Treg and Th17 in LR-subject at cART initiation, no alteration of Treg/Th17 ratio was observed. While polifunctional profile of CD4 T-cells was not different, frequencies of CD4 T-cells producing cytokine-combinations including IL17a were increased in LR-subjects. CONCLUSION: Increased frequencies of Th17, IL17a-producing Treg and CD4 T-cells producing specific IL17a-containing combinations of cytokines, precede the immunodiscordant response to cART, suggesting a potential contribution of these subsets in such anomalous response to cART.
BACKGROUND: Despite the fact that antiretroviral therapy (cART) suppresses HIV-viremia, an adequate CD4 T-cell recovery is not always achieved (immunodiscordant response to cART). IL17a-producing CD4 T-cells (Th17) constitutes an important subset involved in the preservation of mucosal surfaces integrity, which depletion has been associated with disease progression in HIV-infection. However, whether Th17 frequency at cART initiation is associated with a poor CD4 T-cell recovery has not been yet explored. Our aim was to explore whether the Th17 cells and other IL17a-producing T-cell subsets at cART initiation were associated with a subsequent immunodiscordant response to cART. METHODS: We selected pre-cART samples of antiretroviral-naïve subjects with and without a low CD4 recovery after cART (LR-subjects and HR-subjects, respectively). Peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/ionomycine, and the production of several cytokines including IL17a was analyzed by flow cytometry. RESULTS: A trend to higher Th17 (p = 0.05) and increased frequencies of IL17a-producing Treg (p = 0.011) was found in LR-subjects before cART onset. Despite increased frequencies of both Treg and Th17 in LR-subject at cART initiation, no alteration of Treg/Th17 ratio was observed. While polifunctional profile of CD4 T-cells was not different, frequencies of CD4 T-cells producing cytokine-combinations including IL17a were increased in LR-subjects. CONCLUSION: Increased frequencies of Th17, IL17a-producing Treg and CD4 T-cells producing specific IL17a-containing combinations of cytokines, precede the immunodiscordant response to cART, suggesting a potential contribution of these subsets in such anomalous response to cART.
Authors: Isaac Rosado-Sánchez; Inés Herrero-Fernández; Miguel Genebat; Jorge Del Romero; Melchor Riera; Daniel Podzamczer; Julián Olalla; Francesc Vidal; Mª Angeles Muñoz-Fernández; Manuel Leal; Yolanda M Pacheco Journal: Front Immunol Date: 2018-07-18 Impact factor: 7.561
Authors: Isaac Rosado-Sánchez; Rebeca De Pablo-Bernal; Anna Rull; Juan Gónzalez; Santiago Moreno; David Vinuesa; Vicente Estrada; María Ángeles Muñoz-Fernández; Francesc Vidal; Manuel Leal; Yolanda María Pacheco Journal: Front Immunol Date: 2020-11-06 Impact factor: 7.561