Altered T cell differentiation associated with loss of CD27 and CD28 in HIV infected Indian individuals

Background: HIV-1 infection is associated with depletion of naïve T cell subsets and skewed T cell differentiation and maturation, leading to accumulation of T cells at intermediate and end stages of differentiation. CD27 and CD28 expression have been utilized in assessing these population subsets. Methods: We characterized T cell subsets based on expression of CD45RA, CCR7, CD27, and CD28 and compared these subsets in HIV-1 infected Indian subjects and uninfected controls. Results: HIV-1 infection was associated with an increase in effector and memory T cell subsets and a concomitant decrease in naïve T cells. HIV-1 infected subjects showed accumulation of intermediate CD8 T cell (CD27+CD28-) differentiation subsets, whereas CD4 T cells progressed to late stage differentiation (CD27-CD28-). These subsets were negatively associated with CD4 T cell counts and positively associated with plasma viremia. CD57, an immunosenescence marker, was also increased on T cell subsets from HIV-1 infected individuals. Antiretroviral therapy resulted in partial restoration of differentiation status. Conclusion: Persistent HIV-1 replication and chronic immune activation, along with altered cytokine secretion profile, lead to impaired T cell differentiation and maturation. Detailed understanding of factors associated with differentiation defects in HIV-1 infected Indian individuals will strongly assist in Indian HIV-1 vaccine efforts and add to our knowledge of HIV-1 subtype C pathogenesis.