title: Role of innate and acquired immune mechanisms in clinical intestinal transplant rejection.
abstract: BACKGROUND
  Long-term outcomes of intestinal transplantation are limited by infection and rejection. To understand the underlying immune mechanisms, graft infiltrating and peripheral blood cells were analyzed using multiple ex vivo assays in intestinal transplantation recipients.
  
  
  METHODS
  Infiltrating cells from rejected (graft enterectomy for rejection) and accepted or quiescent (stoma closure in stable transplant recipients) grafts were isolated and phenotypically characterized as to subsets and Toll-like receptor expressions as well as functionally tested for antimicrobial and antidonor immune responses. Multiparameter antidonor immunity was also assessed serially in the peripheral blood.
  
  
  RESULTS
  The graft infiltrating lymphocytes were mostly of recipient origin in all patients tested. In rejecting grafts, the predominant populations were TcRαβ(+)CD3(+)CD8(+) T cells, and CD14(+) monocytes that coexpressed Toll-like receptor-2, receptor-3, receptor-4, receptor-5, and receptor-9, suggesting innate immune activation. In quiescent allografts the major cell subsets were CD13(+)CD14(-) monocytes and CD4(+)CD25(+) T cells with possible regulatory functions. Infiltrating cells from rejected but not quiescent grafts proliferated in response to enteric bacterial and donor antigens as well as killed donor targets. Serial follow-up of peripheral blood indicated donor-specific posttransplant unresponsiveness in micro-cell-mediated lympholysis (m-CML) and mixed lymphocyte reaction (MLR) in recipients with quiescent grafts, but not in recipients with multiple rejection episodes. Enzyme-Linked ImmunoSpot assays yielded parallel results: granzyme-B with micro-cell-mediated lympholysis and interferon-γ with MLR tests.
  
  
  CONCLUSIONS
  These results were consistent with the notion that rejection was associated with innate and acquired antimicrobial and antidonor immune reactivity and that patients with stable grafts were free from these deleterious effects.
authors.affiliation: 1 Department of Surgery, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL. 2 Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL. 3 Jesse Brown VA Medical Center, Chicago, IL. 4 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL. 5 Department of Microbiology-Immunology, University of Miami Miller School of Medicine, Miami, FL. 6 Miami VA Medical Center, Miami, FL. 7 Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: James M
authors.initials: JM
authors.lastname: Mathew
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tryphonopoulos
authors.forename: Werviston
authors.initials: W
authors.lastname: DeFaria
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: Joshua
authors.initials: J
authors.lastname: Miller
authors.forename: Terrence A
authors.initials: TA
authors.lastname: Barrett
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakis
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kato
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000918:Antibody Specificity; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000637:transplantation*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014019:Tissue Donors; D051193:Toll-Like Receptors / Q000378:metabolism; D055815:Young Adult
chemical_list: D051193:Toll-Like Receptors; D007371:Interferon-gamma; D053804:Granzymes