ASSOCIATION OF T-CELL AND MACROPHAGE DYSFUNCTION WITH SURFACE GP120-IMMUNOGLOBULIN COMPLEMENT COMPLEXES IN HIV-INFECTED PATIENTS

The mechanism of CD4+ cell depletion and functional T helper cell inhi bition in HIV-infected individuals is poorly understood. The present s tudy demonstrates that immune complex-covered CD4+ cells are associate d with T cell inhibition and macrophage stimulation. We studied 30 pat ients with ARC/AIDS and 35 asymptomatic HIV+ haemophilia patients. Ove rall, 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 lymph ocyte proliferation was associated with the immune complex load of CD4 + cells. The higher the percentage of CD4+ gp120+ cells in the blood, the lower the T cell response in vitro (P = 0.001). Moreover, an assoc iation was found between immune complex-positive cells and plasma neop terin (P=0.01). Patients with increased plasma neopterin levels had de creased in vitro responses to pokeweed mitogen (PWM) (P=0.006), phytoh aemagglutinin (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 gp 1 20 that binds to uninfe cted CD4+ cells. Our data suggest that the functional inhibition and s ubsequent elimination of uninfected CD4+ lymphocytes with surface gp12 0-immunoglobulin-complement complexes may be a pathomechanism in the m anifestation of AIDS.