title: Cutting edge: CD4 T cells reactive to an islet amyloid polypeptide peptide accumulate in the pancreas and contribute to disease pathogenesis in nonobese diabetic mice.
abstract: We previously reported a peptide KS20 from islet amyloid polypeptide (IAPP) to be the target Ag for a highly diabetogenic CD4 T cell clone BDC-5.2.9. To track IAPP-reactive T cells in NOD mice and determine how they contribute to the pathogenesis of type 1 diabetes, we designed a new I-Ag7 tetramer with high affinity for BDC-5.2.9 that contains the peptide KS20. We found that significant numbers of KS20 tetramer(+) CD4 T cells can be detected in the pancreas of prediabetic and diabetic NOD mice. To verify pathogenicity of IAPP-reactive cells, we sorted KS20 tetramer(+) cells and cloned them from uncloned T cell lines isolated from spleen and lymph nodes of diabetic mice. We isolated a new KS20-reactive Th1 CD4 T cell clone that rapidly transfers diabetes. Our results suggest that IAPP triggers a broad autoimmune response by CD4 T cells in NOD mice.
authors.affiliation: Integrated Department of Immunology, University of Colorado at Denver School of Medicine and National Jewish Health, Denver, CO 80206.
authors.forename: Rocky L
authors.initials: RL
authors.lastname: Baker
authors.forename: Thomas
authors.initials: T
authors.lastname: Delong
authors.forename: Gene
authors.initials: G
authors.lastname: Barbour
authors.forename: Brenda
authors.initials: B
authors.lastname: Bradley
authors.forename: Maki
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kathryn
authors.initials: K
authors.lastname: Haskins
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D058228:Islet Amyloid Polypeptide / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology; D011236:Prediabetic State / Q000276:immunology*; D013154:Spleen / Q000166:cytology
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen; D058228:Islet Amyloid Polypeptide
references.citation: Nat Immunol. 2010 Mar;11(3):225-31
references.pmid: 20139986
references.citation: J Exp Med. 2011 Jan 17;208(1):81-90
references.pmid: 21220453
references.citation: Biochem Biophys Res Commun. 1998 Sep 18;250(2):271-7
references.pmid: 9753619
references.citation: J Autoimmun. 2000 Jun;14(4):343-51
references.pmid: 10882061
references.citation: J Exp Med. 2010 Aug 2;207(8):1701-11
references.pmid: 20660617
references.citation: J Immunol. 2011 May 1;186(9):5039-45
references.pmid: 21505216
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14596-601
references.pmid: 11106373
references.citation: J Immunol. 1999 Aug 1;163(3):1205-13
references.pmid: 10415015
references.citation: Int Immunol. 2002 Dec;14(12):1439-47
references.pmid: 12456592
references.citation: Diabetes. 2011 Sep;60(9):2325-30
references.pmid: 21734016
references.citation: Eur J Immunol. 2012 Mar;42(3):672-80
references.pmid: 22488364
references.citation: Diabetes. 2012 Dec;61(12):3239-46
references.pmid: 22912420
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16729-34
references.pmid: 21949373
references.citation: J Immunol. 2005 Dec 1;175(11):7738-45
references.pmid: 16301684
references.citation: Diabetes Metab Res Rev. 2011 Nov;27(8):778-83
references.pmid: 22069259
references.citation: J Immunol. 2000 Jun 1;164(11):5788-96
references.pmid: 10820257
references.citation: J Clin Invest. 2003 Sep;112(6):902-14
references.pmid: 12975475
references.citation: Diabetologia. 1992 Nov;35(11):1080-6
references.pmid: 1473619
references.citation: J Immunol. 2012 Mar 15;188(6):2477-82
references.pmid: 22389204
references.citation: Immunity. 2000 Jun;12(6):699-710
references.pmid: 10894169
references.citation: Proc Natl Acad Sci U S A. 1989 Oct;86(20):8000-4
references.pmid: 2510155
references.citation: Diabetes. 2003 Nov;52(11):2647-51
references.pmid: 14578281
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17040-5
references.pmid: 17942684
references.citation: Adv Immunol. 2005;87:123-62
references.pmid: 16102573