title: The role of direct presentation by donor dendritic cells in rejection of minor histocompatibility antigen-mismatched skin and hematopoietic cell grafts.
abstract: BACKGROUND
  The success of transplantation is hampered by rejection of the graft by alloreactive T cells. Donor dendritic cells (DC) have been shown to be required for direct priming of immune responses to antigens from major histocompatibility complex-mismatched grafts. However, for immune responses to major histocompatibility complex-matched, minor histocompatibility (H) antigen mismatched grafts, the magnitude of the T-cell response to directly presented antigens is reduced, and the indirect pathway is more important. Therefore, we aimed to investigate the requirement for donor DC to directly present antigen from minor H antigen mismatched skin and hematopoietic grafts.
  
  
  METHODS
  Langerhans cell- or conventional (c)DC-depleted skin or hematopoietic cells from male DC-specific diphtheria toxin receptor mice were grafted onto, or injected into, syngeneic female recipients, and survival of the male tissue was compared with nondepleted tissue. Activation of the alloreactive immune response was tracked by the expansion of T cells specific for male HY-derived epitopes.
  
  
  RESULTS
  Our data demonstrate that depletion of donor Langerhans cell, dermal cDC, or both from skin grafts prolongs their survival but does not prevent rejection. Extended survival correlates with delayed expansion of HY peptide-specific CD8 T cells. In addition, depletion of donor cDC delays rejection of male hematopoietic cells.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that direct presentation of minor H antigens by donor DC is required for efficient rejection of skin and hematopoietic grafts by CD8 T cells. But, in the absence of donor DC, indirect presentation of minor antigens is sufficient to mediate the response.
authors.affiliation: Section of Immunobiology, Division of Immunology and Inflammation, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandes
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Goold
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Julian
authors.initials: J
authors.lastname: Dyson
authors.forename: Clare L
authors.initials: CL
authors.lastname: Bennett
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006182:H-Y Antigen / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D066257:Heparin-binding EGF-like Growth Factor; D007165:Immunosuppression Therapy / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007801:Langerhans Cells / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008297:Male; D037241:Mannose-Binding Lectins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D014019:Tissue Donors; D023001:Transplantation Tolerance / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D039521:CD11c Antigen; C498497:Cd207 protein, mouse; D006182:H-Y Antigen; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D015778:Minor Histocompatibility Antigens