title: Accelerated antibody-mediated graft loss of rodent pancreatic islets after pretreatment with dexamethasone-treated immature donor dendritic cells.
abstract: BACKGROUND
  Allogeneic islets of Langerhans transplantation is hampered in its success as a curative treatment of type 1 diabetes by the absence of potent, specific, and nontoxic immunosuppressive drugs. Here, we assessed whether donor bone marrow-derived dexamethasone-treated dendritic cells (dexDCs) could prolong islet allograft survival in a full major histocompatibility complex mismatch rat model.
  
  
  METHODS
  Rodent allogeneic islet transplantation was performed from DA rats to Lewis rats and vice versa. Permanently immature dendritic cells were generated from the bone marrow of DA and Lewis rats by treatment with dexamethasone. Animals were either vehicle or donor dexDCs pretreated. Serum was used to monitor glucose, C-peptide, and alloreactive antibodies.
  
  
  RESULTS
  The transplantation of DA islets into Lewis recipients showed direct graft failure with reduced numbers of β-cells when rats were pretreated with donor dexDCs. In the reverse model (Lewis islets into DA recipients), dexDC-treated DA recipients even showed a significantly accelerated rejection of Lewis islets. Immunohistochemical analysis of allograft tissue of dexDC-treated recipients showed a predominant natural killer cell infiltration and a presence of antibody reactivity in the absence of complement deposition. Alloreactive antibodies were solely found in dexDC-treated recipients.
  
  
  CONCLUSIONS
  Our study shows that pretreatment with donor-derived dexDCs induces an antibody-mediated rejection in this islet transplantation rodent model.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: de Kort
authors.forename: Cynthia
authors.initials: C
authors.lastname: Crul
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: van der Wal
authors.forename: Nicole
authors.initials: N
authors.lastname: Schlagwein
authors.forename: Annelein M
authors.initials: AM
authors.lastname: Stax
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D002465:Cell Movement / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation*; D003907:Dexamethasone / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000473:pathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000009:adverse effects; D013601:T-Lymphocytes / Q000473:pathology; D013997:Time Factors
chemical_list: D000906:Antibodies; D013311:Streptozocin; D003907:Dexamethasone