PT  - JOURNAL ARTICLE
AU  - Endl, Josef
AU  - Rosinger, Silke
AU  - Schwarz, Barbara
AU  - Friedrich, Sven-Olaf
AU  - Rothe, Gregor
AU  - Karges, Wolfram
AU  - Schlosser, Michael
AU  - Eiermann, Thomas
AU  - Schendel, Dolores J.
AU  - Boehm, Bernhard O.
TI  - Coexpression of CD25 and OX40 (CD134) Receptors Delineates Autoreactive T-cells in Type 1 Diabetes
AID  - 10.2337/diabetes.55.01.06.db05-0387
DP  - 2006 Jan 01
TA  - Diabetes
PG  - 50--60
VI  - 55
IP  - 1
4099  - http://diabetes.diabetesjournals.org/content/55/1/50.short
4100  - http://diabetes.diabetesjournals.org/content/55/1/50.full
SO  - Diabetes2006 Jan 01; 55
AB  - T-cell–mediated loss of pancreatic β-cells is the crucial event in the development of type 1 diabetes. The phenotypic characteristics of disease-associated T-cells in type 1 diabetes have not yet been defined. The negative results from two intervention trials (the Diabetes Prevention Trial–Type 1 Diabetes and the European Nicotinamide Diabetes Intervention Trial) illustrate the need for technologies to specifically monitor ongoing autoimmune reactions. We used fluorescence-activated cell sorter analysis to study surface marker expression on T-cell lines specific for two major type 1 diabetes autoantigens, GAD65 and proinsulin. We then applied this knowledge in a cross-sectional approach to delineate the phenotype of circulating memory T-cells. The autoreactive T-cells of patients could be distinguished from those of control subjects by their coexpression of CD25 and CD134. Autoantigen-specific T-cells that recognized multiple GAD65- and preproinsulin-derived peptides and coexpressed CD25+CD134+ were confined to patients (n = 32) and pre-diabetic probands (n = 5). Autoantigen-reactive T-cells in control subjects (n = 21) were CD25+CD134− and recognized fewer autoantigen-derived peptides. Insulin therapy did not induce CD25+CD134+ T-cells in type 2 diabetic patients. The coexpression of CD25 and the costimulatory molecule CD134 on memory T-cells provides a novel marker for type 1 diabetes–associated T-cell immunity. The CD134 costimulatory molecule may also provide a novel therapeutic target in type 1 diabetes.