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 and intraepithelial lymphocytes (IELs) in the rat. They exhibit both adenosine diphosphoribosyltransferase and nicotine adenine dinucleotide (NAD) glycohydrolase activities, and both can generate a transmembrane signal that modulates T cell activation. The presence or absence of ART2+ T cells modulates the expression of autoimmune diabetes in the BB rat. ART2 also circulates 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 rats 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 (BBDP/Wor) rat. In diabetes-resistant BB (BBDR/Wor) rats, administration of anti-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 sustained supraphysiologic levels of soluble ART2a. Although the number of peripheral ART2a+ T cells is known to correlate with the expression of diabetes in BBDR/Wor rats, the level of soluble ART2a protein did not. The source of the soluble ART2 protein in the rat appeared to be the gut. The results suggest that ART2+ T cells and soluble ART2 protein may subserve different immunomodulatory functions.
Bortel
R
R
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA. Rita.Bortell@umassmed.edu
Waite
D J
DJ
Whalen
B J
BJ
Todd
D
D
Leif
J H
JH
Lesma
E
E
Moss
J
J
Mordes
J P
JP
Rossini
A A
AA
Greiner
D L
DL
D036002:ADP Ribose Transferases; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000918:Antibody Specificity; D000945:Antigens, Differentiation, T-Lymphocyte; D015551:Autoimmunity; D018956:CD5 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D005260:Female; D006649:Histocompatibility Antigens / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains; D011923:Rats, Nude; D012995:Solubility; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018956:CD5 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases; C090163:Art2b protein, rat; D009244:NAD+ Nucleosidase