title: Induction of acute GVHD by sex-mismatched H-Y antigens in the absence of functional radiosensitive host hematopoietic-derived antigen-presenting cells.
abstract: It is currently thought that acute GVHD cannot be elicited in the absence of Ag presentation by radiosensitive host hematopoietic-derived APCs after allogeneic BM transplantation. Because clinical data suggest that sex-mismatched H-Y Ags may be important minor histocompatibility Ags for GVH responses, we directly tested their relevance and ability to initiate GVHD when presented by either the hematopoietic- (host or donor) or the nonhematopoietic-derived APCs. H-Y minor Ag incompatibility elicited both CD4(+) and CD8(+) T-cell driven GVHD lethality. Studies with various well-established BM chimera recipients, in contrast to the current views, have reported that in the absence of functional radiosensitive host hematopoietic-derived APCs, H-Y Ag presentation by either the donor hematopoietic-derived or the host nonhematopoietic-derived APCs is sufficient for inducing GVHD. Our data further suggest that infusion of sufficient numbers of alloreactive donor T cells will induce GVHD in the absence of radiosensitive host hematopoietic-derived APCs.
authors.affiliation: Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Toubai
authors.forename: Isao
authors.initials: I
authors.lastname: Tawara
authors.forename: Yaping
authors.initials: Y
authors.lastname: Sun
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Evelyn
authors.initials: E
authors.lastname: Nieves
authors.forename: Rebecca
authors.initials: R
authors.lastname: Evers
authors.forename: Thea
authors.initials: T
authors.lastname: Friedman
authors.forename: Robert
authors.initials: R
authors.lastname: Korngold
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
mesh_terms: D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000628:therapy*; D006182:H-Y Antigen / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011836:Radiation Tolerance; D013934:Thymectomy
chemical_list: D006182:H-Y Antigen; D007519:Isoantigens
references.citation: J Clin Invest. 1998 Dec 1;102(11):1933-41
references.pmid: 9835618
references.citation: J Clin Invest. 2003 Dec;112(12):1880-6
references.pmid: 14679183
references.citation: Transplantation. 1996 Feb 27;61(4):619-24
references.pmid: 8610390
references.citation: J Immunol. 2006 Mar 15;176(6):3383-90
references.pmid: 16517706
references.citation: Nat Med. 2002 Jun;8(6):575-81
references.pmid: 12042807
references.citation: Annu Rev Immunol. 1997;15:39-61
references.pmid: 9143681
references.citation: Blood. 2002 Mar 1;99(5):1825-32
references.pmid: 11861301
references.citation: Blood. 2010 Dec 16;116(25):5738-47
references.pmid: 20807889
references.citation: Blood. 2004 Jan 1;103(1):347-52
references.pmid: 12969970
references.citation: Blood. 2011 Jan 13;117(2):697-707
references.pmid: 20944073
references.citation: J Immunol. 2010 Oct 1;185(7):3866-72
references.pmid: 20810991
references.citation: J Immunol. 2001 Mar 15;166(6):3846-54
references.pmid: 11238628
references.citation: Blood. 2009 Dec 3;114(24):5062-70
references.pmid: 19828695
references.citation: J Clin Invest. 1996 Aug 1;98(3):622-8
references.pmid: 8698852
references.citation: J Immunol. 2001 Oct 1;167(7):3756-64
references.pmid: 11564792
references.citation: Nat Med. 2004 May;10(5):510-7
references.pmid: 15098028
references.citation: J Exp Med. 2004 Apr 19;199(8):1133-42
references.pmid: 15096539
references.citation: Blood. 1997 Oct 15;90(8):3204-13
references.pmid: 9376604
references.citation: Transplantation. 1999 Jul 15;68(1):141-9
references.pmid: 10428282
references.citation: Blood. 2011 Jul 7;118(1):192-204
references.pmid: 21471527
references.citation: Blood. 2010 Jan 21;115(3):724-35
references.pmid: 19965670
references.citation: Nat Med. 2005 Nov;11(11):1222-9
references.pmid: 16227989
references.citation: Biol Blood Marrow Transplant. 2011 Dec;17(12):1747-53
references.pmid: 21871863
references.citation: Biol Blood Marrow Transplant. 2004 Apr;10(4):224-35
references.pmid: 15077221
references.citation: J Clin Invest. 1998 Jul 1;102(1):115-23
references.pmid: 9649564
references.citation: J Exp Med. 2003 Oct 6;198(7):1089-102
references.pmid: 14517277
references.citation: J Clin Invest. 2008 Jul;118(7):2562-73
references.pmid: 18568076
references.citation: Blood. 2006 Sep 15;108(6):2106-13
references.pmid: 16757687
references.citation: Blood. 2005 Apr 1;105(7):2973-8
references.pmid: 15613541
references.citation: J Exp Med. 1978 Dec 1;148(6):1687-98
references.pmid: 363972
references.citation: Blood. 2003 Jul 15;102(2):429-35
references.pmid: 12663438
references.citation: Science. 1999 Jul 16;285(5426):412-5
references.pmid: 10411505
references.citation: Blood. 2002 Sep 1;100(5):1903-9
references.pmid: 12176915
references.citation: J Immunol. 1994 Dec 15;153(12):5402-12
references.pmid: 7989746
references.citation: Biol Blood Marrow Transplant. 1997 Jun;3(2):57-64
references.pmid: 9267665
references.citation: Biol Blood Marrow Transplant. 2006 Aug;12(8):818-27
references.pmid: 16864052
references.citation: Immunity. 2003 Mar;18(3):367-79
references.pmid: 12648454
references.citation: Biol Blood Marrow Transplant. 2010 Sep;16(9):1222-30
references.pmid: 20338255
references.citation: Nat Med. 2001 Jul;7(7):789-94
references.pmid: 11433342
references.citation: Blood. 2011 Dec 1;118(23):6209-19
references.pmid: 21768295
references.citation: Nat Med. 2005 Nov;11(11):1244-9
references.pmid: 16227991
references.citation: Curr Protoc Immunol. 2001 May;Chapter 3:Unit 3.19
references.pmid: 18432783
references.citation: Nat Immunol. 2002 Sep;3(9):844-51
references.pmid: 12172545
references.citation: Blood. 2002 Apr 15;99(8):3027-32
references.pmid: 11929796
references.citation: Science. 1995 Sep 15;269(5230):1588-90
references.pmid: 7667640