Fas-induced apoptosis is a rare event in Sjögren's syndrome

Abstract

The aim of this study was to perform a controlled in situ analysis on the incidence of apoptosis, investigate the expression of apoptosis-mediating proteins, and determine the frequency of apoptotic CD4+ and CD8+ T cells in Sjögren's syndrome (SS). The study was extended to patients with atrophy-fibrosis (AF) not related to SS, as well as to a control group. Immunohistochemistry and the terminal deoxynucleotidyl transferase mediated dUTP digoxigenin nick end labeling (TUNEL) method were applied to study the Fas and FasL expression and the incidence of apoptosis in salivary glands (SG) from patients with primary and secondary SS, AF, and controls. These methods were also combined to enable simultaneous detection of apoptotic and CD4+ or CD8+ T cells. Despite abundant expression of Fas and FasL in SS SG, apoptotic cells were not exceeding 1% in the foci of infiltrating mononuclear cells (IMC). Double staining showed that the frequency of apoptosis was low among both CD4+ and CD8+ T cells. Only a few TUNEL+ epithelial cells were found in all patient groups. Fas was expressed predominantly on SS IMC, single SS epithelial cells, and a few normal acinar cells, but not in AF SG. Although FasL was present on SS and AF IMC and epithelial cells, it was rarely detected in normal tissue. Consequently we demonstrate that Fas-induced apoptosis among SS SG is a rare event. Our findings support an earlier hypothesis indicating that IMC seem to be able to escape apoptosis, resulting in foci of inflammatory cells. Notably, however, no obvious correlation can be drawn to previous studies where a high incidence of apoptosis of epithelial cells was proposed as an important mechanism leading to decreased glandular function, which is a hallmark of SS.