Fig. 1

Suppression of peripheral T cells by soluble molecular forms of Fas, including the full-length receptor (sFas), and sequential 8-mer peptides structurally related to its first consensus sequence including VEINCTR-N, an immunogenic epitope. (A) Prevalent inhibition of the proliferative rate was observed after 48 hr in T-cell cultures from 16 human immunodeficiency virus-type 1 (HIV-1)-infected individuals (full symbols) selected from a group of patients with serum elevations of both anti-VEINCTR-N immunoglobulin G (IgG) and soluble Fas (sFas), and increased extent of T-cell apoptosis (7). Inhibition of ³H-thymidine uptake was significant in cultures treated with either sFas or VEINCTR-N (p < 0.02 in all instances), and in those with pept. #2 (p < 0.1), compared with relative control unstimulated cultures whose values of ³H-thymidine uptake were referred as 100% of proliferation. Control T-cell cultures from 15 uninfected subjects (empty symbols) were inhibited prevalently by sFas, though to a lesser degree. Such a suppressive effect of sFas was abolished in control cultures by its preincubation with ZB4 MoAb. Values are expressed as percentages of ³H-thymidine uptake. (B) Cytofluorimetric patterns of apoptosis induction by both sFas and VEINCTR-N in peripheral T cells from an HIV-1-infected patient (upper panels) and a normal donor (lower panels), measured as variation of M1, namely the subdiploid DNA-containing cell population, following propidium iodide staining. A significant increase of M1 occurred at 48 hr of culture in cells treated with either sFas or VEINCTR-N, compared with untreated control cells (p < 0.02 in both groups of experiments). By contrast, pept. #1 and #2 failed to induce appreciable changes in most cell preparations.