title: Hyperexpression of Foxp3 and IDO during acute rejection of islet allografts.
abstract: BACKGROUND
  We investigated the hypothesis that Foxp3+ cells are an integral component of antiallograft immunity but are dominated by pathogenic effectors.
  
  
  METHODS
  Wild-type H-2b C57BL/6 (B6) mice or B6 mice with a targeted disruption of c-Rel gene (c-Rel-/-) were used as recipients of islet grafts from allogeneic DBA/2 (H-2d) mice or syngeneic B6 mice. We developed kinetic quantitative polymerase chain reaction assays and measured intragraft expression of mRNA for Foxp3, IDO, cytolytic molecules, proinflammatory cytokines, and chemokines/receptors.
  
  
  RESULTS
  Intraislet levels of mRNA for Foxp3, IDO, CD3, CD25, tumor necrosis factor-alpha, RANTES, IP-10, and CXCR3 were highest in DBA/2 islet allografts from WT B6 recipients compared to DBA/2 islet allografts from c-Rel-/- B6 recipients or syngeneic B6 islet grafts from WT B6 mice. The ratio of granzyme B or IFN-gamma to Foxp3 was higher with the DBA/2 islet allografts from the WT B6 recipients compared to DBA/2 islet allografts from c-Rel-/- B6 recipients or B6 islet grafts from WT B6 recipients.
  
  
  CONCLUSIONS
  Foxp3+ cells are an integral component of acute rejection of allografts but may be dominated by pathogenic effectors.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10021, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Ruchuang
authors.initials: R
authors.lastname: Ding
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Fludd Saint
authors.initials: FS
authors.lastname: Hilaire
authors.forename: Milagros
authors.initials: M
authors.lastname: Lagman
authors.forename: Baogui
authors.initials: B
authors.lastname: Li
authors.forename: Dolca A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Dolea A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Xunrong
authors.initials: X
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.forename: Craig
authors.initials: C
authors.lastname: Stauffer
authors.forename: Phyllis
authors.initials: P
authors.lastname: August
authors.forename: Manikkam
authors.initials: M
authors.lastname: Suthanthiran
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006084:Graft Rejection / Q000473:pathology*; D053804:Granzymes / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D016381:Islets of Langerhans Transplantation / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D053804:Granzymes