Granule associated DNase in T4 and T8 lymphocytes from patients with autoimmune diseases

Abstract

The presence of a DNase activity associated with secretion granules was detected in T4 and T8 lymphocytes from patients with autoimmune diseases. This activity was much higher in primary biliary cirrhosis (PBC) than in Graves' disease (GD) and multiple sclerosis (MS) or in healthy subjects. This granule associated DNase activity was Ca 2+-dependent, inhibited by Zn 2+, and higher at low pH; its molecular weight corresponded to 66 kDa; it was more active with double-strand than single-strand DNA. Judging from its properties this enzyme differed from the three types of endonucleases described as involved in DNA fragmentation (DNase 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 +CD45RO +/CD4 +CD45RA + (memory and cytotoxic cells/naive cells, inducers of suppression). In contrast, T8 lymphocyte DNase activity correlated with the proportion of CD4 + lymphocytes with CD4 +CD45RA − phenotype (helpers and inducers of cytotoxicity). The possible role of this DNase activity in the mechanisms of lysis or apoptosis mediated by CTL is discussed. We suggest that this DNase activity could be implicated in some of the alterations of the autoimmune response depending on cytotoxic T lymphocytes or T cell inducers of apoptosis.