Levels of Art2(+) cells but not soluble Art2 protein correlate with expression of autoimmune diabetes in the BB rat

ART2a and ART2b are isoenzymes expressed on the surface of mature T cells a nd intraepithelial lymphocytes (IELs) in the rat. They exhibit both adenosi ne diphosphoribosyltransferase and nicotine adenine dinucleotide (NAD) glyc ohydrolase activities, and both can generate a transmembrane signal that mo dulates T cell activation. The presence or absence of ART2(+) T cells modul ates the expression of autoimmune diabetes in the BB rat. ART2 also circula tes in a soluble. form whose function is unknown. We tested the hypothesis that circulating ART2 protein regulates the expression of autoimmunity. We compared the kinetics, regulation, and source of soluble ART2 in normal rat s and in rats with autoimmune diabetes. Basal levels of soluble ART2 varied greatly among strains of rats-and were lowest in the diabetes-prone BB (BB DP/Wor) rat. In diabetes-resistant BB (BBDR/Wor) rats, administration of an ti-ART2a antibody, which is known to induce diabetes, resulted in transient clearing of soluble ART2a that was followed rapidly by a rebound increase. Repeated treatment of BBDR/Wor rats with anti-ART2a antibody resulted in s ustained supraphysiologic levels of soluble ART2a. Although the number of p eripheral ART2a(+) T cells is known to correlate with the expression of dia betes in BBDR/Wor rats, the level of soluble ART2a protein did not. The sou rce of the soluble ART2 protein in the rat appeared to be the gut. The resu lts suggest that ART2(+) T cells and soluble ART2 protein may subserve diff erent immunomodulatory functions.