title: Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production.
abstract: BACKGROUND
  Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs) stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs) and plasmacytoid (pDCs) are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown.
  
  
  METHODS
  Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2(d)) prior to transplanting into C57BL/6 mice (H-2(b)), followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+).
  
  
  RESULTS
  Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production.
  
  
  CONCLUSIONS
  Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.
authors.affiliation: Department of Medicine, Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Benson
authors.forename: Hidemi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Jeremy
authors.initials: J
authors.lastname: Lott
authors.forename: Amanda Jo
authors.initials: AJ
authors.lastname: Fisher
authors.forename: Crystal
authors.initials: C
authors.lastname: Walline
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Heidler
authors.forename: Randy
authors.initials: R
authors.lastname: Brutkiewicz
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D016040:Lung Transplantation / Q000473:pathology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines