Intestinal mucosa represents an important portal of entry of HIV and a site of virus reservoir and active replication. Recently, in HIV patients, an early depletion of intestinal lamina propria T lymphocytes (LPT) has been described. HIV-1 gp120 has been demonstrated to promote apoptosis in noninfected isolated peripheral blood T cells, therefore we investigated whether gpl20 modulates apoptosis of normal human intestinal lamina propria T cells. Purified T cells were obtained by immunomagnetic negative selection from human lamina propria mononuclear cells isolated from surgical specimens by enzymatic procedure. Cells were incubated with or without recombinant gpl20 (10 microg/ml) and cultured either in the absence of any stimulus or in the presence of plate-bound anti-CD3 Ab (OKT3) or soluble anti-CD2 Ab (T11(2) + T11[3]). Apoptosis was assessed by flow cytometric analysis after propidium iodide staining. We demonstrated that preincubation of normal LPT cells with HIV-1 gpl20 accelerates the apoptosis observed during CD2-pathway stimulation of LPT cells. This process is mediated by Fas/Fas ligand interaction and related to an increased induction of Fas ligand mRNA by gpl20. Therefore HIV-1 gp120 could contribute to the depletion of noninfected LPT cells inducing a premature cell death.