title: Trachea allograft class I molecules directly activate and retain CD8+ T cells that cause obliterative airways disease.
abstract: Human T cells responding against transplanted allogeneic lung tissue have been implicated in late graft failure secondary to obliterative bronchiolitis. This obliterative airways disease (OAD) also develops in heterotopic murine tracheal allografts in association with graft infiltration by both CD8(+) and CD4(+) T cells. To date, there has been little evidence to suggest that directly alloreactive CD8(+) T cells either promote chronic rejection or lead to the development of OAD following airway allotransplantation. Using L(d)-specific TCR-Tg 2C CD8(+) T cells adoptively transferred into wild-type B6 (H-2(b)) mice and the transplantation of BALB/c (H-2(d)) tracheal allografts, we now show that the direct recognition of donor-specific class I MHC molecules by host CD8(+) T cells leads to their activation, clonal expansion within the graft, and differentiation to an effector phenotype with the capacity to induce airway fibrosis. In addition, these experiments demonstrate that ongoing direct alloantigen recognition within the transplanted airway tissue is necessary for the recruitment and retention of these directly alloreactive CD8(+) T cells. Thus, these experiments are the first to definitively show a role for directly alloreactive CD8(+) T cells in the chronic rejection that leads to OAD.
authors.affiliation: Department of Medicine and. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Richards
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Dalheimer
authors.forename: Marshall I
authors.initials: MI
authors.lastname: Hertz
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mueller
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005355:Fibrosis; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000502:physiology*; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013045:Species Specificity; D014132:Trachea / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000276:immunology* / Q000473:pathology
chemical_list: D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma