title: Identification of CD3+CD4-CD8- T cells as potential regulatory cells in an experimental murine model of graft-versus-host skin disease (GVHD).
abstract: We have developed K14-mOVA transgenic (Tg) mice that express membrane-associated ovalbumin (mOVA) under the control of a K14 promoter, as well as double Tg mice, by crossing them with OT-I mice that have a TCR recognizing the OVA peptide. When injected with CD8(+) OT-I cells, K14-mOVA Tg mice develop graft-versus-host disease (GVHD), whereas double Tg mice are protected. This suggests that, in double Tg mice, regulatory mechanisms may prevent infused OT-I cells from inducing GVHD. We demonstrated that, after adoptive transfer, TCRαβ(+)CD3(+)CD4(-)CD8(-)NK1.1(-) double-negative (DN) T cells are increased in the peripheral lymphoid organs and skin of double Tg mice and exhibit a Vα2(+)Vβ5(+)TCR that has the same TCR specificity as OT-I cells. These DN T cells isolated from tolerant double Tg mice proliferated in response to OVA peptide and produced IFN-γ in the presence of IL-2. These cells could also suppress the proliferation of OT-I cells and were able to specifically kill activated OT-I cells through Fas/Fas ligand interaction. These findings suggest that DN T cells that accumulate in double Tg mice have regulatory functions and may have a role in the maintenance of peripheral tolerance in vivo.
authors: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Fumi
authors: F
authors: Miyagawa
authors: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Naoko
authors: N
authors: Okiyama
authors: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Vadim
authors: V
authors: Villarroel
authors: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: katzs@od.niams.nih.gov.
authors: Stephen I
authors: SI
authors: Katz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D012871:Skin Diseases / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D007371:Interferon-gamma; D010047:Ovalbumin
references: Nature. 1988 Jun 23;333(6175):742-6
references: 3260350
references: J Exp Med. 2002 Jul 15;196(2):261-7
references: 12119351
references: Eur J Immunol. 2011 Mar;41(3):739-48
references: 21287552
references: Nature. 1989 Nov 30;342(6249):559-61
references: 2573841
references: Hum Immunol. 2002 Oct;63(10):926-34
references: 12368045
references: J Immunol. 2003 Feb 15;170(4):1846-53
references: 12574350
references: J Immunol. 2004 Sep 1;173(5):3112-8
references: 15322171
references: J Invest Dermatol. 2004 Jul;123(1):109-15
references: 15191550
references: Adv Immunol. 2011;112:137-76
references: 22118408
references: Nat Immunol. 2001 Dec;2(12):1117-25
references: 11713466
references: Nat Rev Immunol. 2002 Jan;2(1):11-9
references: 11908514
references: J Immunol. 2001 Dec 1;167(11):6188-94
references: 11714779
references: Br J Haematol. 2008 Apr;141(2):170-8
references: 18318770
references: Science. 1991 Mar 8;251(4998):1225-8
references: 1900951
references: J Immunol. 2008 Jul 15;181(2):1109-19
references: 18606663
references: Nat Rev Immunol. 2003 Mar;3(3):233-42
references: 12658271
references: Nat Med. 2000 Jul;6(7):782-9
references: 10888927
references: Immunity. 2000 Dec;13(6):829-40
references: 11163198
references: Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12123-8
references: 22783014
references: Blood. 2005 Apr 1;105(7):2828-35
references: 15572590
references: Cell. 1987 Apr 24;49(2):273-80
references: 3494522
references: Eur J Immunol. 2002 Jun;32(6):1584-92
references: 12115641
references: Cell. 2008 May 30;133(5):775-87
references: 18510923
references: J Immunol. 2005 Sep 1;175(5):3409-16
references: 16116235
references: Blood. 2007 May 1;109(9):4071-9
references: 17197428
references: J Immunol. 2009 Sep 1;183(5):3130-8
references: 19675167
references: J Mol Med (Berl). 2002 May;80(5):290-300
references: 12021841
references: Eur J Immunol. 2007 Aug;37(8):2234-41
references: 17578845
references: Immunol Cell Biol. 2010 Nov-Dec;88(8):771-80
references: 20603635
references: Science. 1990 Dec 21;250(4988):1726-9
references: 2125368
references: J Invest Dermatol. 2012 Mar;132(3 Pt 1):677-86
references: 22089830
references: Annu Rev Immunol. 2000;18:185-216
references: 10837057
references: J Autoimmun. 2010 Nov;35(3):192-8
references: 20655706
references: Eur J Immunol. 2011 Sep;41(9):2699-708
references: 21660936
references: J Immunol. 2003 Jul 1;171(1):134-41
references: 12816991