title: New strategies for early diagnosis of heart allograft rejection.
abstract: BACKGROUND
  Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition).
  
  
  METHODS
  T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+ LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays.
  
  
  RESULTS
  Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes.
  
  
  CONCLUSIONS
  Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.
authors.affiliation: Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tugulea
authors.forename: R
authors.initials: R
authors.lastname: Ciubotariu
authors.forename: A I
authors.initials: AI
authors.lastname: Colovai
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Itescu
authors.forename: L L
authors.initials: LL
authors.lastname: Schulman
authors.forename: P E
authors.initials: PE
authors.lastname: Fisher
authors.forename: M A
authors.initials: MA
authors.lastname: Hardy
authors.forename: E A
authors.initials: EA
authors.lastname: Rose
authors.forename: R E
authors.initials: RE
authors.lastname: Michler
authors.forename: R
authors.initials: R
authors.lastname: Cortesini
authors.forename: N
authors.initials: N
authors.lastname: Suciu-Foca
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006684:HLA-DR Antigens / Q000737:chemistry / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000379:methods; D007700:Kinetics; D008285:Major Histocompatibility Complex; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D010446:Peptide Fragments