title: Alloimmune response results in expansion of autoreactive donor CD4+ T cells in transplants that can mediate chronic graft-versus-host disease.
abstract: Chronic graft-versus-host disease (cGVHD) is considered an autoimmune-like disease mediated by donor CD4(+) T cells, but the origin of the autoreactive T cells is still controversial. In this article, we report that the transplantation of DBA/2 donor spleen cells into thymectomized MHC-matched allogeneic BALB/c recipients induced autoimmune-like cGVHD, although not in control syngeneic DBA/2 recipients. The donor-type CD4(+) T cells from the former but not the latter recipients induced autoimmune-like manifestations in secondary allogeneic BALB/c as well as syngeneic DBA/2 recipients. Transfer of donor-type CD4(+) T cells from secondary DBA/2 recipients with disease into syngeneic donor-type or allogeneic host-type tertiary recipients propagated autoimmune-like manifestations in both. Furthermore, TCR spectratyping revealed that the clonal expansion of the autoreactive CD4(+) T cells in cGVHD recipients was initiated by an alloimmune response. Finally, hybridoma CD4(+) T clones derived from DBA/2 recipients with disease proliferated similarly in response to stimulation by syngeneic donor-type or allogeneic host-type dendritic cells. These results demonstrate that the autoimmune-like manifestations in cGVHD can be mediated by a population of donor CD4(+) T cells in transplants that simultaneously recognize Ags presented by both donor and host APCs.
authors.affiliation: Department of Diabetes Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Dongchang
authors.initials: D
authors.lastname: Zhao
authors.forename: James S
authors.initials: JS
authors.lastname: Young
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shen
authors.forename: Tangsheng
authors.initials: T
authors.lastname: Yi
authors.forename: Ivan
authors.initials: I
authors.lastname: Todorov
authors.forename: Peiguo G
authors.initials: PG
authors.lastname: Chu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Defu
authors.initials: D
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002908:Chronic Disease; D002999:Clone Cells; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006183:H-2 Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D023421:Models, Animal; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell