Association of T cell and macrophage dysfunction with surface gp 120-immunoglobulin-complement complexes in HIV-infected patients.
The mechanism of CD4+ cell depletion and functional T helper cell inhibition in HIV-infected individuals is poorly understood. The present study demonstrates that immune complex-covered CD4+ cells are associated with T cell inhibition and macrophage stimulation. We studied 30 patients with ARC/AIDS and 35 asymptomatic HIV+ haemophilia patients. Overall, 20 +/- 3% of peripheral CD4+ lymphocytes were covered with gp120 (range 0-94%). gp120+ cells also exhibited surface-bound IgG (P = 0.0001), IgM (P = 0.0001), and complement (P = 0.0001). Decreased in vitro lymphocyte proliferation was associated with the immune complex load of CD4+ cells. The higher the percentage of CD4+ gp 120+ cells in the blood, the lower the T cell response in vitro (P = 0.001). Moreover, an association was found between immune complex-positive cells and plasma neopterin (P = 0.01). Patients with increased plasma neopterin levels had decreased in vitro responses to pokeweed mitogen (PWM) (P = 0.006), phytohaemagglutinin (PHA) (P = 0.004), concanavalin A (Con A) (P = 0.09), and anti-CD3 MoAb (P = 0.03), and decreased CD4+ cell counts in the blood (P = 0.006). Since maximally 1% of CD4+ lymphocytes are infected with HIV, T cell dysfunction and T cell depletion in HIV-infected patients may also be caused by the release of free gp120 that binds to uninfected CD4+ cells. Our data suggest that the functional inhibition and subsequent elimination of uninfected CD4+ lymphocytes with surface gp120-immunoglobulin-complement complexes may be a pathomechanism in the manifestation of AIDS.
Daniel
V
V
Department of Transplantation Immunology, University of Heidelberg, Germany.
Süsal
C
C
Weimer
R
R
Zimmermann
R
R
Huth-Kühne
A
A
Opelz
G
G
D000936:Antigen-Antibody Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000936:Antigen-Antibody Complex; D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D003165:Complement System Proteins