The mechanism by which human immunodeficiency virus 1 (HIV-1) infection causes increased rates of apoptosis and gradual chronic depletion of CD4(+) T lymphocytes in patients infected with HIV-1 is not known. Findings from in vitro culture studies and analysis of mononuclear cells in the peripheral blood of HIV-infected patients have led to the hypothesis that abnormal expression and/or interaction of Fas and Fas ligand (FasL) may play significant roles in the derangement of homeostasis of CD4(+) lymphocytes in patients infected with HIV-1.
To determine the in situ expression of Fas and FasL in the lymph nodes of patients infected with HIV-1.
Immunohistochemical expression of Fas and FasL was studied in the lymph node biopsy specimens from 20 patients infected with HIV-1. As controls, we also studied 120 lymph nodes from 28 HIV-1-seronegative patients with reactive lymphadenopathy.
In the reactive lymph nodes of seronegative patients, expression of Fas was diffuse in the germinal centers and also in immunoblast-like cells in the T-cell regions. In the lymph nodes of patients infected with HIV, there was a consistent remarkable decrease in Fas expression in 12 of 20 patients and a total lack of Fas expression in the remaining 8 patients. Expression of FasL was comparable in both patient groups.
There is marked down-regulation of Fas in the lymph nodes of HIV-infected patients, a sharp contrast to what occurs in circulating mononuclear cells in the peripheral blood of these patients. These results indicate the need for further studies of this molecular event for possible therapeutic intervention based on reconstitution of Fas and/or FasL activity in the treatment of HIV infection.