GRANULE-ASSOCIATED DNASE IN T4 AND T8 LYMPHOCYTES FROM PATIENTS WITH AUTOIMMUNE-DISEASES

The presence of a DNase activity associated with secretion granules wa s detected in T4 and T8 lymphocytes from patients with autoimmune dise ases. This activity was much higher in primary biliary cirrhosis (PBC) than in Graves' disease (GD) and multiple sclerosis (MS) or in health y subjects. This granule associated DNase activity was Ca2+-dependent, inhibited by Zn2+, and higher at low pH; its molecular weight corresp onded to 66kDa; it was more active with double-strand than single-stra nd DNA. Judging from its properties this enzyme differed from the thre e types of endonucleases described as involved in DNA fragmentation (D Nase I, DNase II and NUC18). Flow cytometry analysis of T lymphocytes showed that DNase activity associated with CD4(+) lymphocyte granules correlated with the ratio CD4(+)CD35RO(+)/CD4(+)CD45RA(+) (memory and cytotoxic cells/naive cells, inducers of suppression). In contrast, Ts lymphocyte DNase activity correlated with the proportion of CD4(+) ly mphocytes with CD4(+)CD45RA(-) phenotype (helpers and inducers of cyto toxicity). The possible role of this DNase activity in the mechanisms of lysis or apoptosis mediated by CTL is discussed. We suggest that th is DNase activity could be implicated in some of the alterations of th e autoimmune response depending on cytotoxic T lymphocytes or T cell i nducers of apoptosis. (C) 1998 Elsevier Science B.V.