title: Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity.
abstract: Transgenic (Tg) mouse models of autoimmunity have been used to express model antigens that can be recognized by T cells or by autoantibodies. To identify mechanisms of CD8-mediated tissue-specific autoimmune reactions and to identify potential treatments, we generated a double-transgenic (DTg) murine model of autoimmunity by crossing keratin-14 (K14)-soluble chicken ovalbumin (sOVA) mice, which express sOVA predominantly in external ear skin, with OT-I mice whose CD8 T cells express Vα2/Vβ5 regions of the TCR and are specific for SIINFEKL peptide (chicken ovalbumin (OVA) peptide 257-264) in association with class I major histocompatibility complex. The K14-sOVA/OT-I DTg mice develop a destructive process selectively targeting the external ear pinnae in the first 6 days of life. The ear bud area develops an intense inflammatory infiltrate of OT-I cells. Administration of the SIINFEKL peptide intravenously to pregnant F1 (filial 1, first filial generation of animal offspring from cross-mating two parental types) mice and subsequently intraperitoneally to newborn pups resulted in normal external ear development. Treatment with this self-peptide markedly reduced OT-I cell numbers, as well as downregulated the CD8 co-receptor. This model can be useful in studying localized, tissue-specific, immune-mediated skin disease, and provide information about potential therapies for autoimmune diseases in which specific molecular targets are known.
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Paek
authors.forename: Fumi
authors.initials: F
authors.lastname: Miyagawa
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Jay T
authors.initials: JT
authors.lastname: Linton
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Hoover
authors.forename: R Mark
authors.initials: RM
authors.lastname: Simpson
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Katz
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D053547:Keratin-14 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012871:Skin Diseases / Q000188:drug therapy*
chemical_list: C067361:CD8 receptor; D053547:Keratin-14; C507446:Krt14 protein, mouse; C110366:OVA-8; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin
references.citation: J Immunol. 1998 Nov 15;161(10):5260-7
references.pmid: 9820498
references.citation: J Immunol. 2002 Aug 15;169(4):2141-7
references.pmid: 12165543
references.citation: Curr Opin Allergy Clin Immunol. 2009 Aug;9(4):316-21
references.pmid: 19474709
references.citation: Immunity. 1997 May;6(5):519-29
references.pmid: 9175830
references.citation: Nat Med. 2005 Apr;11(4 Suppl):S69-76
references.pmid: 15812493
references.citation: Nat Immunol. 2007 Oct;8(10):1049-59
references.pmid: 17873878
references.citation: Eur J Dermatol. 2010 Mar-Apr;20(2):236-8
references.pmid: 20110201
references.citation: J Immunol. 2009 Sep 1;183(5):3130-8
references.pmid: 19675167
references.citation: Immunol Today. 1997 Dec;18(12):599-604
references.pmid: 9425739
references.citation: Nature. 1996 Jan 25;379(6563):343-6
references.pmid: 8552189
references.citation: J Autoimmun. 2010 Nov;35(3):192-8
references.pmid: 20655706
references.citation: Br J Dermatol. 1989 Apr;120(4):541-4
references.pmid: 2659064
references.citation: Nat Rev Immunol. 2008 Dec;8(12):970-6
references.pmid: 19008897
references.citation: J Immunol. 2000 Jul 1;165(1):202-10
references.pmid: 10861053
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1338-43
references.pmid: 9037054
references.citation: Nat Immunol. 2000 Oct;1(4):336-41
references.pmid: 11017106
references.citation: Curr Opin Immunol. 2005 Dec;17(6):624-31
references.pmid: 16226438
references.citation: Immunity. 2002 Jul;17(1):1-6
references.pmid: 12150886
references.citation: J Invest Dermatol. 2004 Jul;123(1):109-15
references.pmid: 15191550
references.citation: J Exp Med. 1997 Nov 17;186(10):1663-76
references.pmid: 9362527
references.citation: J Oral Pathol Med. 2010 Nov;39(10):729-34
references.pmid: 20923445
references.citation: Immunol Rev. 2005 Apr;204:116-27
references.pmid: 15790354
references.citation: Eur J Immunol. 1998 May;28(5):1626-35
references.pmid: 9603469
references.citation: J Invest Dermatol. 1984 Apr;82(4):326-8
references.pmid: 6368699