title: Sclerodermatous chronic graft-versus-host disease induced by host T-cell-mediated autoimmunity.
abstract: Despite a long-standing hypothesis that chronic graft-versus-host disease (cGVHD) is an autoimmune disorder, most mouse models of cGVHD have been developed on the assumption that donor T cells are essential for its development. Here we show that cGVHD may be caused by autoreactive host T cells in mice that have been lethally irradiated and grafted with T-cell-depleted allogeneic bone marrow cells. In this chimera, host T cells derived from radioresistant intrathymic T-cell precursors caused dermal fibrosis and periportal inflammation, without the requirement for donor T cells. The lack of host DCs within the thymus after high-dose irradiation allowed autoreactive host T cells to escape thymic negative selection. Moreover, the homeostatic expansion of these T cells may augment their autoreactivity. These findings indicate that host T-cell-mediated cGVHD is an autoimmune process that occurs following the grafting of T-cell-depleted BM cells into hosts with functioning thymuses. We propose, based on the present data, that host T-cell-dependent autoimmunity is a potential mechanism by which cGVHD is induced.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: You Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Kang
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Hong Gyun
authors.initials: HG
authors.lastname: Wu
authors.forename: Eun-Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Seong Hoe
authors.initials: SH
authors.lastname: Park
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
mesh_terms: D000818:Animals; D015551:Autoimmunity; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002908:Chronic Disease; D060966:Clonal Selection, Antigen-Mediated; D003713:Dendritic Cells / Q000276:immunology*; D006086:Graft vs Host Disease / Q000150:complications / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D045745:Scleroderma, Limited / Q000209:etiology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D018183:Transplantation Chimera