Diabetes induced with low doses of streptozotocin is mediated by V beta 8.2+ T-cells

• Published in: Diabetes (New York, N.Y.) Vol. 44; no. 3; pp. 354 - 359
• Main Authors: Herold, K C, Bloch, T N, Vezys, V, Sun, Q
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-03-1995
• Subjects: Animals; Base Sequence; Causes of; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - pathology; DNA Primers; Dose-Response Relationship, Drug; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Physiological aspects; Polymerase Chain Reaction; Receptor-CD3 Complex, Antigen, T-Cell - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Spleen - immunology; Streptozocin - administration & dosage; Streptozocin - toxicity; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Time Factors; Type 1 diabetes
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.44.3.354

Diabetes induced with low doses of streptozotocin is mediated by V beta 8.2+ T-cells.
K C Herold ,
T N Bloch ,
V Vezys and
Q Sun
Department of Medicine, University of Chicago, Illinois 60637.
Abstract
T-cells have been shown to cause insulitis and ultimately be responsible for the destruction of beta-cells in animal models
of insulin-dependent diabetes mellitus (IDDM). In one murine model, insulitis and hyperglycemia occur after administration
of five low doses of streptozotocin (STZ) (multidose STZ-induced diabetes mellitus [MDSM]). Insulitis can first be identified
in the islets after the final (fifth) daily dose of STZ is given. We have studied the T-cells that infiltrate the islets of
Langerhans during the early stages of diabetes by preparing Southern blots of T-cell receptor (TCR) beta-chain genes amplified
by polymerase chain reaction (PCR) from islets from C57BL/KsJ mice given multiple doses of STZ. The relative abundance of
TCR gene products in islets was compared with spleen cells stimulated with anti-CD3 monoclonal antibody (mAb). We found that
after the fourth dose of STZ, there was a striking increase in the amount of V beta 8.2 TCR gene product (37 +/- 4% of total
PCR signal) compared with T-cells in the spleen (9 +/- 2%, P < 0.01), which increased further 2 days after the final dose
of STZ (47 +/- 5%, P < 0.001). We studied the heterogeneity of the size of the V beta 8.2 TCR CDR3 region and found primarily
products with only two lengths compared with a heterogeneous population in the spleen. Treatment with anti-V beta 8 mAb, but
not anti-V beta 9 and anti-V beta 13 mAbs, prevented development of hyperglycemia (P < 0.0001) and insulitis (P < 0.0005)
after STZ administration.