title: The early course of kidney allograft rejection: defining the time when rejection begins.
abstract: We studied the early events in mouse kidney allografts and isografts to define when allorecognition begins and when alloimmune tissue injury begins. Allografts but not isografts showed T-cell infiltration in perivascular areas from day 1, but tubulitis and arteritis did not develop until day 7. Flow cytometry confirmed the early allospecific CD3(+)CD8(+) T-cell infiltrate. At day 1, both allografts and isografts showed extensive transcriptome changes, reflecting the response to surgery, but only allografts showed expression of interferon-gamma (IFN-gamma)-inducible transcripts and T-cell-associated transcripts. Although the number of CD68(+) myeloid cell numbers did not increase in day 1 isografts or allografts, mRNA expression for myeloid markers was increased in isografts and allografts, suggesting activation of resident cells of the macrophage-dendritic cell series (MMDCs) in response to injury, followed by increased CD68(+) cell numbers from day 2. By day 3, an interstitial T-cell and MMDC infiltrate was established in allografts, corresponding with the emergence of allospecific tissue injury, as reflected by decreased parenchymal transcripts. Thus, in renal allografts, allorecognition by T cells occurs in perivascular sites by day 1, but alloimmune parenchymal damage begins at day 3, coinciding with the emergence of the interstitial T-cell-MMDC infiltrate.
authors.affiliation: Department of Medicine, Division of Nephrology and Transplantation Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Einecke
authors.forename: M
authors.initials: M
authors.lastname: Mengel
authors.forename: L
authors.initials: L
authors.lastname: Hidalgo
authors.forename: K
authors.initials: K
authors.lastname: Allanach
authors.forename: K S
authors.initials: KS
authors.lastname: Famulski
authors.forename: P F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D007371:Interferon-gamma