title: Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival.
abstract: Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; ib234@columbia.edu.
authors: Ibrahim
authors: I
authors: Batal
authors: Renal Division, Schuster Family Transplantation Research Center, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; and.
authors: Sacha A
authors: SA
authors: De Serres
authors: Renal Division, Schuster Family Transplantation Research Center, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; and.
authors: Kassem
authors: K
authors: Safa
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
authors: Vanesa
authors: V
authors: Bijol
authors: Renal Division, Schuster Family Transplantation Research Center, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; and.
authors: Takuya
authors: T
authors: Ueno
authors: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Maristela L
authors: ML
authors: Onozato
authors: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors: A John
authors: AJ
authors: Iafrate
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
authors: Jan M
authors: JM
authors: Herter
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
authors: Andrew H
authors: AH
authors: Lichtman
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
authors: Tanya N
authors: TN
authors: Mayadas
authors: Renal Division, Schuster Family Transplantation Research Center, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; and.
authors: Indira
authors: I
authors: Guleria
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
authors: Helmut G
authors: HG
authors: Rennke
authors: Renal Division, Schuster Family Transplantation Research Center, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; and.
authors: Nader
authors: N
authors: Najafian
authors: Renal Division, Schuster Family Transplantation Research Center, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; and.
authors: Anil
authors: A
authors: Chandraker
mesh_terms: D000328:Adult; D064591:Allografts / Q000276:immunology / Q000473:pathology*; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000032:analysis*; D003713:Dendritic Cells / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation; D037181:Lectins, C-Type / Q000032:analysis*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009393:Nephritis / Q000473:pathology; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000032:analysis*; D013601:T-Lymphocytes / Q000473:pathology / Q000648:ultrastructure; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: chronic graft deterioration; chronic inflammation; transplant pathology