Preserved immune functionality and high CMV-specific T-cell responses in HIV-infected individuals with poor CD4⁺...

Poor CD4⁺ T-cell recovery after cART has been associated with skewed T-cell maturation, inflammation and immunosenescence; however, T-cell functionality in those individuals has not been fully characterized. In the present study, we assessed T-cell function by assessing cytokine production after polyclonal, CMV and HIV stimulations of T-cells from ART-suppressed HIV-infected individuals with CD4⁺ T-cell counts >350 cells/μL (immunoconcordants) or <350 cells/μL (immunodiscordants). A group of HIV-uninfected individuals were also included as controls. Since CMV co-infection significantly affected T-cell maturation and polyfunctionality, only CMV⁺ individuals were analyzed. Despite their reduced and skewed CD4⁺ T-cell compartment, immunodiscordant individuals showed preserved polyclonal and HIV-specific responses. However, CMV response in immunodiscordant participants was significantly different from immunoconcordant or HIV-seronegative individuals. In immunodiscordant subjects, the magnitude of IFN-γ⁺ CD8⁺ and IL-2⁺ CD4⁺ T-cells in response to CMV was higher and differently associated with the CD4⁺ T-cell maturation profile., showing an increased frequency of naïve, central memory and EMRA CMV-specific CD4⁺ T-cells. In conclusion, CD4⁺ and CD8⁺ T-cell polyfunctionality was not reduced in immunodiscordant individuals, although heightened CMV-specific immune responses, likely related to subclinical CMV reactivations, may be contributing to the skewed T-cell maturation and the higher risk of clinical progression observed in those individuals.