Changing patterns of cell surface mono (ADP-ribosyl) transferase antigen ART2.2 on resting versus cytopathically-activated T cells in NOD/Lt mice

Aims/hypothesis. ART2.2 is a mouse T-cell surface ectoenzyme [mono (ADP-rib osyl) transferase] shed upon strong activation. We analysed temporal change s in ART2.2 expression in unmanipulated and clophosphamide-treated NOD/Lt m ice compared with diabetes-resistant control strains. We used NAD, the ART2 .2 substrate, to test whether ART-mediated ADP-ribosylation could retard di abetogenic activation of islet-reactive T cells in vitro. Methods. ART2.2 and CD38, another NAD-utilizing enzyme, were measured by fl ow cytometry. ADS-ribosylation from ethano-NAD was followed by flow cytomet ry using a reagent specific for etheno-ADP ribose. Results. Although mature NOD CD4 + and CD8 + T cells expressed ART2.2, this expression was delayed in young NOD mice when compared with control strain s. This ontological delay at 3 weeks of age correlated with an early burst of CD25 expression unique to NOD splenic T cells, This pattern was reproduc ed in cyclophosphamide-accelerated diabetes in young NOD/Lt males, wherein a retarded repopulation of ART2.2 T cells in spleen and islets correlated w ith development of heavy insulitis and diabetes. NAD inhibited anti-CD3 ind uced:activation of splenic T cells in vitro and also retarded killing of be ta-cell targets by NOD islet-reactive CD8 effecters in vitro at concentrati ons equal to or greater than 1 mu mol/l. Evidence suggested that CD38 on B lymphocytes competes with ART2.2 for substrate needed by B lymphocytes for ADP ribosylation. Conclusions. ART2.2 on T cells may not simply mark the resting state, but c ould also contribute to it via ADP-ribosylation.