Identification of CD8+ T cell subsets that normalize in early-treated people living with HIV receiving antiretroviral therapy

ABSTRACT:Background: Although combined antiretroviral therapy (cART) has decreased the mortality associated with HIV infection, complete immune reconstitution is not achieved despite viral suppression. Alterations of CD8+ T cells and some of their subpopulations, such as interleukin (IL)-17-producing cells, are evidenced in treated individuals and are associated with systemic infammation and adverse disease outcomes. We sought to evaluate if diferent CD8+ T cell subsets are diferentially normalized during a clinical follow-up of people living with HIV (PLWH) receiving suppressive cART. Methods: We explored the changes in the frequencies, activation/exhaustion phenotypes (HLA-DR, CD38, PD-1, and TIM-3), and function (total and HIV-specifc cells expressing CD107a, perforin, granzyme B, interferon [IFN]-γ and IL-17) of CD8+ T cells from early-treated PLWH receiving cART in a 1-year follow-up, using a multidimensional fow cytom‑ etry approach. Results: Despite continuous cART-induced viral suppression and recovery of CD4+ T cells, after a 1-year follow-up, the CD8+ T cell counts, CD4:CD8 ratio, PD-1 expression, and IL-17 production by CD8+ T cells exhibited incomplete normalization compared with seronegative controls. However, the proportion of CD8+ T cells with an exhausted phenotype (co-expressing PD-1 andTIM-3), and cells co-expressing cytotoxic molecules (Perforin and Granzyme B), reached normalization. Conclusions: Although suppressive cART achieves normalization of CD4+ T cell counts, only particular subsets of CD8+ T cells are more rapidly normalized in PLWH receiving cART, which could be routinely used as biomarkers for therapy efciency in these patients

• Autores: Rugeles López, María Teresa; Velilla Hernández, Paula Andrea; Díaz Castrillón, Francisco Javier; Taborda Vanegas, Natalia Andrea; Perdomo Celis, Federico; Arcia Anaya, David; Alzate, Juan Carlos; Posada, María Paulina
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2022
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/35559
• Acceso en línea: https://hdl.handle.net/10495/35559
• Palabra clave: Linfocitos T CD8-positivos; CD8-Positive T-Lymphocytes; Granzimas; Granzymes; Infecciones por VIH; HIV Infections; Reconstitución Inmune; Immune Reconstitution; Receptor de Muerte Celular Programada 1; Programmed Cell Death 1 Receptor; Receptores de Interleucina-17; Receptors, Interleukin-17
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/