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

Abstract

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.

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

“…Few previous studies evaluated CMV-specific polyfunctionality in PLWHIV, but recently, maintained polyfunctionality was found in CMV-specific terminally differentiated T-cells from ART-naïve PLWHIV 60 , and in CMV-specific memory CD4+ T-cells from long-term nonprogressors despite inflation of these cells 61 . In accordance with our results, a very recent study showed maintained CMV-specific T-cell polyfunctionality despite phenotypic T-cell alterations in PLWHIV treated with cART 62 . The importance of maintained polyfunctionality is still debated, and an important consideration is, that polyfunctionality may not necessarily be beneficial in PLWHIV, if accompanied by increased immune pathology or tissue damage through high release of cytokines.…”

Seroprevalence of Cytomegalovirus Infection Among HIV-Infected and HIV-Uninfected Pregnant Women Attending Antenatal Clinic in Harare, Zimbabwe

“…We suspect that since there is a massive production of IgG antibodies during a secondary immune response to a pathogen, there could be reactivation of CMV resulting in the surge of anti-CMV IgG production (27). However, due to compromised immunity especially in the HIV-infected individuals and immune senescence associated with HIV and CMV itself, there may be failure to mount an IgM immune response, sufficient to be detected by the ELISA (15). This results in underestimation of active CMV infection.…”

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…Total CD4 + T-cell count > 400 cells/µl at 2 years after ART initiation, with plasma HIV RNA < 50 copies/ml. 48,105,106,241 Total CD4 + T-cell count < 350 cells/µl and/or increase in the CD4 + T-cell count < 30% from baseline at 1-10 years after ART initiation, with an undetectable plasma VL.…”