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Islet-derived CD4 T-cells targeting proinsulin in human autoimmune diabetes


, : Islet-derived CD4 T-cells targeting proinsulin in human autoimmune diabetes. Diabetes (): -

NlmCategory="UNASSIGNED">Type 1 diabetes results from chronic autoimmune destruction of insulin-producing beta cells within pancreatic islets. While insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T-cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T-cells from type 1 diabetes patients. We identified hundreds of T-cells from inflamed pancreatic islets of three young type 1 diabetes organ donors with a short disease duration with high risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture. Among 85 selected CD4 TCRs tested for reactivity to preproinsulin peptides presented by diabetes-susceptible HLA-DQ and -DR molecules, one T-cell recognized C-peptide amino acids 19-35, and two clones from separate donors responded to insulin B chain amino acids 9-23 (B:9-23) which is known to be a critical self-antigen driving disease progress in animal models of autoimmune diabetes. These B:9-23-specific T-cells from islets responded to whole proinsulin and islets, while previously identified B:9-23 responsive clones from peripheral blood did not, highlighting the importance of proinsulin-specific T-cells in the islet microenvironment.

US$19.90

PMID: 27920090

DOI: 10.2337/db16-1025


Other references

Bax, J.J.; Cornel, J.H.; Visser, F.C.; Fioretti, P.M.; Van Lingen, A.; Valkema, R.; Visser, C.A., 1998: Improvement of specificity of thallium-201 rest-redistribution to predict functional outcome after revascularization. Journal of Nuclear Medicine 39(5 SUPPL ): 60P, May

Sakai, T., 1994: Psychosomatic analysis of laryngectomized patients. The psychosocial influences of laryngectomy were evaluated in patients with head and neck cancer. Five patients who had indications for surgery, refused laryngectomy. They preferred their occupational activities and pleasure in their social lives...

Soar, C.D., 1897: Some Notes on Hydrachnidae. Jtt Club: 318-321

Fumihik, T.Naka, Y.Shihir, K.Nishi, Y.Zur, K.Roki, D.Isuk, H.Manaka, T.Shitak, U.Hino, 2012: The use of cfd to improve the performance of a partially loaded cold store. A transient three-dimensional computational fluid dynamics model was developed to investigate the cooling performance of a partially loaded cold store in cooling process. The model accounted for turbulence by means of the standard k-? model with s...

Jarayaman, A.; Clark, E.D.B.rnardez; Goldberg, E., 1995: Effects of heat and SDS on the structure and function of bacteriophage T4 P12 protein. Abstracts of Papers American Chemical Society 209(1-2): BIOT 111

Udovenko, G.V.; Smirnova, V.S., 1986: The formation of yield components following exposure to low temperatures in winter wheat varieties differing in frost resistance. Plants of 5 cultivars were exposed to temperatures from -7 to -19 degrees C in a controlled climate chamber during the period of declining frost resistance (the end of March). The qualitative effects of these low temperatures on subsequent growth...

Desmond, J.E., 2010: Trends in cerebellar research. Behavioural Neurology 23(1-2): 1-2

Schrader J.; Haddy F.J.; Gerlach E., 1976: Release of carbon 14 adenosine from the guinea pig heart during auto regulation. Harris, Peter, Richard J Bing And Albrecht Fleckenstein (Ed ) Recent Advances in Studies on Cardiac Structure And Metabolism, Vol 7 Biochemistry And Pharmacology Of Myocardial Hypertrophy, Hypoxia, And Infarction Proceedings Of The Sixth Annual Meeting Freiburg, West Germany, Sept 25-28, 1973 Xi+489p Illus University Park Press: Baltimore, Md , U S A ; London, England Isbn 0-8391-0667-X 171-175

Dunn, E.R.; Conant, R., 1937: The herpetological fauna of Bermuda. Herpetologica Chicago, 1: 78-80

Masuda, O.; Habe, T., 1988: Corbicula insularis Prime established in Kurashiki City, Okayama Pref., Honshu. Chiribotan, 192: 39-40