Increased Peripheral Blood Leukocyte Subsets with Regulatory Phenotype in Clinically Stable Long-Term HIV-Infected Hemophilia Patients on HAART May Be Beneficial and Contribute to a Decrease in Autoimmunity

After initiation of highly-active antiretroviral therapy (HAART), long-term HIV-infected hemophilia patients have been shown to lose autoantibodies against CD4+ peripheral blood leukocytes (PBL), suggesting that HAART induces autoimmunity-blocking mechanisms. We compared cytokine levels and subpopulations of lymphocytes and dendritic cells (DC) in the blood of 40 long-term HIV+ patients with those of 13 long-term HIV– hemophilia patients; 23 HIV+ patients had a detectable retroviral load. Cell subsets were determined using flow cytometry and cytokine levels were measured using ELISA. HIV+ patients showed higher proportions of DC subpopulations with immunostimulatory phenotypes (p < 0.01), CD8+ PBL (p < 0.001), and IL-2 (p < 0.001) and sIL-2R plasma levels (p = 0.002) than HIV– patients. They also exhibited increased proportions of T PBL with immunosuppressive phenotypes such as CD3+CD4+CD25+Foxp3+ (p = 0.001), and CD3+CD8+CD28–Foxp3+ PBL (p < 0.001), and a decreased IL-7R expression on CD3+CD8+ PBL (p = 0.001) compared to HIV– patients. Frequencies of CD3+CD4+CD25+ PBL producing IL-2, IL-4, IL-10, IL-12, and/or IFN-γ, and of CD3+CD4+CD28– PBL secreting IL-2 and/or IL-4 were lower in HIV+ than in HIV– patients (p ≤ 0.02). Proportions of CD4+ PBL coated with IgG, IgM, and C3d were similar in HIV+ and HIV– patients (p = n.s.). However, the proportion of CD4+gp120+ PBL was higher in HIV+ patients (p = 0.002), and associated with low CD3+CD4+CD25+Foxp3+ PBL (p = 0.012). We conclude that long-term HIV-infected hemophilia patients on HAART show an adaptive immune response, presumably against HIV, in the presence of upregulated immunosuppressive T PBL, downregulated cytokine-producing CD4+ PBL, and downregulated IL-7R expression on CD8+ PBL. Increased immunoregulatory T PBL might decrease autoimmunity, thereby contributing to immunological reconstitution and stabilization of long-term HIV-infected hemophilia patients on HAART.