Recovery of HIV-mediated Immune Aging of T Cells in Virologically Controlled HIV-Infected Patients on Antiretroviral Therapy

Abstract

Abstract Several studies have shown that HIV infection induces an accelerated aging of T cells, immunosenescence, and alterations in T cell homeostasis resulting in dysregulation of T cell function and rapid HIV disease progression in infected individuals. We have investigated whether long term antiretroviral therapy (ART), which successfully controls viremia and restores CD4 T cell counts in HIV-infected individuals, is correlated with reversal of immunosenescence and/or improved homeostasis of T cells in 100 virologically controlled HIV-infected individuals. We show that the median frequencies of immunosenescence of T cells (CD4+/CD8+ CD28−, CD27−, CD57+ and CD28−CD57+ T cells), were higher in the HIV-infected cohort than the uninfected cohort, however, senescent T cells significantly decreased with increasing CD4 T cell counts in HIV-infected individuals. Although overall levels of naïve CD4+ and CD8+ T cells were lower in HIV-infected than uninfected individuals, there was a significant increase in both CD4+ and CD8+ naïve T cells with increasing CD4 T cell counts in HIV-infected individuals. In addition, the increase in naïve CD4+ and CD8+ T cells in HIV-infected individuals was due to recent thymic immigrants expressing CD31+ marker; however, with increasing CD4 T cells counts accumulation of CD4+CD31− T cells were seen. Moreover, the CD4+ T cells of HIV-infected individuals produced cytokines, including IL-2, IL-10 and IFN-g comparable to uninfected individuals. In conclusion, HIV-infected individuals with controlled viremia and restored CD4 T cell counts due to prolonged ART showed significant reduction in T cell immunoscenesce and improvement of T cell homeostasis and function.