APOPTOSIS IN LABIAL SALIVARY-GLANDS FROM SJOGRENS-SYNDROME (SS) PATIENTS - COMPARISON WITH HUMAN T-LYMPHOTROPIC VIRUS-I (HTLV-I)-SERONEGATIVE AND (HTLV-I)-SEROPOSITIVE SS PATIENTS

Apoptosis is a type of cell death that occurs during morphogenesis and development of the immune system. One of the mechanisms is mediated t hrough the Fas and Fas ligand (FasL) pathway. To determine the possibl e involvement of Fas and its ligand in salivary gland destruction, we analysed the appearance of nuclei with DNA fragmentation by using nick end labelling (TUNEL) and the expression of Fas and Fast by immunohis tochemistry in labial salivary glands. Furthermore we compared the fea tures of apoptosis in labial salivary glands between HTLV-I- and HTLV- II: SS. When the frozen sections of 10 primary SS patients in the abse nce of anti-HTLV-I antibody were examined, several apoptotic cells wer e found in the acinar and ductal epithelial cells as well as infiltrat ed mononuclear cells. Both Fas and Fast were detected in the infiltrat ed mononuclear cells. Acinar epithelial cells, which are surrounded by FasL(+) mononuclear cells, were also double-positive with Fas and Fas t, although the expression of Fast was localized at their apical borde r, suggesting that apoptosis of mononuclear cells was achieved by acti vation-induced mechanisms through Fas/FasL pathways, and that of acina r epithelial cells was mediated by Fast derived from either acinar epi thelial cells themselves or infiltrated mononuclear cells. Interesting ly, Fas expression in ductal epithelial cells was localized around the lumen side of the ducts, indicating that Fast secreted from acinar ep ithelial cells may induce Fas-mediated apoptosis of ductal epithelial cells. We also studied the labial salivary glands from nine SS patient s with anti-HTLV-I antibodies. There was no significant difference in the occurrence of apoptotic cells or in the expression of Fas and Fast between HTLV-I+ and HTLV-I- SS patients. It was of note that neither the expression of Fas and Fast nor the presence of apoptotic cells wer e determined in labial salivary glands from subjects without SS. These findings indicate that Fas-mediated apoptosis in salivary glands coul d be involved in the pathological manifestations of SS, irrespective o f HTLV-I seropositivity.