209 Emergence of Exhausted B Cells in Asymptomatic HIV-1-Infected Patients Naïve for HAART is Related to Reduced Immune Surveillance

Abstract

HIV-1 infection induces a general status of perturbation on immune system cells leading patients to be susceptible to opportunistic infections and tumours. Immune cells of HIV-1-infected patients show several functional defects associated to the chronic cell-hyperactivation and cell-exhaustion. Most of these impairments characterize advanced stage of HIV-1 disease (CD4+ T cell lymphopenia and ongoing HIV-1 replication). To investigate if signs of B cells exhaustion and impaired viral immune-surveillance were present in asymptomatic HIV-1-infected patients with preserved CD4+ T cell counts and Highly Active Antiretroviral Therapy (HAART)-untreated. Forty-three asymptomatic HAART-untreated HIV-1-infected patients were evaluated for immunological parameters defining immune exhaustion of B cells, and for Torque Teno Virus (TTV) viral load. Twenty aviremic HAART-treated patients and 34 healthy individuals were used as control groups. Peripheral blood samples were analyzed by flow cytometry for the identification of B cell subpopulations. IL-7 serum levels were quantified by ELISA. TTV viral load was determined by real-time PCR. Mann-Whitney U-test and Spearman rank correlation coefficient test were used for statistical analysis. Asymptomatic HIV-1-infected patients showed dramatic expansion of exhausted tissue-like memory B cells, which correlated with HIV-1 and TTV viral loads. They also displayed increased IL-7 levels. Normal B cell subsets, IL-7 levels and TTV viral load were observed in aviremic HAART-treated patients. Taken together these results show that asymptomatic HIV-1-infected patients showed the emergence of exhausted B cell elements associated with an impaired control of TTV replication. Successfully HAART-treated patients showed normal B cell subpopulations frequency and TTV viral load. Early application of HAART may prevent the loss of immune functions.