Search

Background and Objectives: Human immunodeficiency virus (HIV)-induced immune complex load on circulating CD4+ blood lymphocytes is associated with dysfunction and depletion of CD4+ lymphocytes and with increased monocyte/macrophage function. It was investigated whether HAART reduces both the viral load in plasma and the number of immune complex-coated CD4+ lymphocytes in the blood, and whether CD4+ counts are associated with viral load and/or immune complex load., Materials and Methods: Twelve HIV+ hemophilia patients before and after conversion to HAART (group 1); eight HIV+ hemophilia patients without antiretroviral therapy (group 2). HIV-1 RNA copies in plasma using NASBA/Nuclisens kits; CD4+ lymphocytes coated in-vivo with immune complexes using flowcytometry on whole blood samples; in-vitro responses of immune complex-coated T lymphocytes in cell culture assays., Results: After conversion to HAART there was a significant reduction of viral load, CD4+ gp120+, CD4+ IgM+, and CD4+ IgG+ circulating blood lymphocytes and plasma neopterin, paralleled by a significant increase of CD4+ and CD8+ counts. The percentage of immune complex-coated CD4+ lymphocytes of converted patients was significantly associated with CD4+ counts, in-vitro responses to concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), anti-CD3 and pooled allogeneic stimulator cells, and with plasma neopterin levels., Conclusion: HAART reduces viral load and HIV-induced immune complex load on circulating CD4+ blood lymphocytes. The results of this study can be interpreted to suggest that HAART increases CD4+ lymphocyte counts in part by counteracting HIV-induced autoimmune phenomena.

Objective: We investigated whether the induction of antilymphocyte autoantibodies and immune complexes is associated with the activity of HIV replication., Methods: Viral HIV-1 RNA was measured in the plasma samples of 84 HIV+ hemophilia patients and correlated with the IgM, IgG, IgM/IgG and IgM/IgG/gp120 load of circulating CD4+ lymphocytes, CD4+ and CD8+ cell counts, plasma neopterin levels and in vitro T-cell responses to mitogens and pooled allogeneic stimulator cells., Results: Compared to patients with no immune complexes, on circulating CD4+ lymphocytes, viral load was increased in patients with IgM, IgM/IgG or IgM/IgG/gp120 complexes. Sequential analysis of HIV+ patients showed that peaks of retroviral activity were associated with the subsequent formation of CD4+ lymphocyte-reactive IgM and IgG autoantibodies and gp120-containing immune complexes., Conclusion: The induction of autoantibodies and immune complexes attached to CD4+ lymphocytes is associated with periods of increased viral activity in HIV-infected patients.

HIV induces progressive dysfunction followed by numerical depletion of CD4+ lymphocytes. IgG autoantibodies and gp 120-containing immune complexes have been implicated in the pathogenesis of AIDS. We carried out a longitudinal study in 19 HIV- and 72 HIV+ haemophilia patients over a 10-year period in order to investigate a possible relationship between the occurrence of autoantibodies and CD4+ lymphocyte changes. IgM, IgG, C3d and gp120 on the surface of CD4+ lymphocytes were determined in heparinized whole blood with flow cytometry and double-fluorescence. The in vitro response of autoantibody-coated cells was tested in cell cultures with concanavalin A (Con A), phytohaemagglutinin (PHA), pokeweed mitogen (PWM) anti-CD3 MoAb or pooled allogeneic stimulator cells (MLC). After a 10-year follow up, 12 of 71 HIV+ and 16 of 19 HIV- haemophilia patients showed no evidence of immunoglobulins on circulating CD4+ lymphocytes. HIV- haemophilia patients without autoantibodies had CD4+ and CD8+ cell counts in the normal range (957+/-642/microliters and 636+/-405/microliters) and normal T cell responses in vitro (mean relative response (RR) > or = 0.7). In contrast, HIV+ haemophilia patients showed immunological abnormalities which were associated with the autoantibody and immune complex load of CD4+ blood lymphocytes. HIV+ patients without autoantibodies had a mean CD4+ lymphocyte count of 372+/-274/microliter, a mean CD8+ lymphocyte count of 737+/-435 microliter, and normal T lymphocyte stimulation in vitro (mean RR > or = 0.7). HIV+ patients with complement-fixing IgM on CD4+ lymphocytes had somewhat lower CD4+ (255+/-246/microliters, P = NS) and CD8+ (706 +/- 468/microliters, P = NS) lymphocyte numbers, and also normal T lymphocyte stimulation (mean RR > or = 0.7) in vitro. However, patients with complement-fixing IgG autoantibodies showed a strong decrease of CD4+ (150 +/- 146/microliters, P< 0.02) and CD8+ (360 +/- 300 microliters, (P<0.02) lymphocytes and impaired CD4+ lymphocyte stimulation in vitro with a mean RR of 0.5+/-0.5 for Con A (P = NS), 0.7 +/- 0.8 for PHA (P<0.03), 0.4 +/- 0.4 for PWM (P = NS), 0.8 +/- 1.2 for anti-CD3 MoAb (P<0.04) and 0.7 +/- 1.0 for pooled allogeneic stimulator cells (P=0.05). Patients with gp120-containing immune complexes on CD4+ blood lymphocytes demonstrated strongly decreased CD4+ (25+/-35/microliters, P<0.0001) and CD8+ (213+/-212/microliters, P<0.006) lymphocyte counts as well as strongly impaired T lymphocyte responses in vitro upon stimulation with PHA (RR 0.2+/-0.1, P<0.02), PWM (RR 0.2+/&#95;0.2, P=0.05), anti-CD3 MoAb(RR 0.1+/-0.1, P<0.04), and allogeneic stimulator cells (RR 0.2+/-0.1, P<0.02). These data led us to speculate that autoantibody formation against CD4+ lymphocytes is an important mechanism in the pathogenesis of AIDS. We hypothesize that autoantibodies against circulating CD4+ lymphocytes inhibit CD4+ cell function, especially the release of cytokines, and induce CD4+ cell depletion. The reduction and dysfunction of CD4+ lymphocytes may be responsible for the CD8+ cell depletion observed in HIV+ patients.