title: T cell-dependent protective effects of CpG motifs of bacterial DNA in experimental colitis are mediated by CD11c+ dendritic cells.
abstract: BACKGROUND
  Oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanosine (CpG) sequence motifs constitute the immunostimulatory components of bacterial DNA which potently activate innate immunity. Administration of CpG-ODNs before the onset of experimental colitis prevents intestinal inflammation by induction of colitis-suppressing T cells.
  
  
  OBJECTIVE
  To identify the interplay between innate and adaptive immune cells finally leading to protective CpG-ODN effects in intestinal inflammation.
  
  
  METHODS
  Total splenic cells or purified selected cell types (CD4(+)CD62L(+) T cells alone or with B cells or dendritic cells (DCs)) from BALB/c mice were (co)-incubated in vitro with CpG-ODN for 5 days and CD4(+)CD62L(+) cells were injected intraperitoneally into C.B.-17 SCID (severe combined immunodeficiency) mice. Splenic CD4(+)CD62L(+) T cells were isolated from transgenic donor mice in which CD11c(+) DCs were depleted by diphtheria toxin administration during CpG-ODN treatment and injected into C57BL/6 Rag2(-/-) recipients. Intestinal inflammation was evaluated by histological scoring and cytokine secretion of mesenteric lymph node cells.
  
  
  RESULTS
  CpG-ODN treatment of total splenic cells but not of purified CD4(+)CD62L(+) cells reduced the colitogenic potential of transferred T cells. While CpG-ODN stimulation of co-cultured CD4(+)CD62L(+) and B-cells did not alter the colitogenic potential of T cells, co-incubation of CpG-ODN-stimulated DCs and CD4(+)CD62L(+) cells reduced the colitogenic potential of the T cell population. Depletion of CD11c(+) DCs during CpG-ODN administration in vivo abolished the protective CpG-ODN effects.
  
  
  CONCLUSIONS
  CpG-ODN-dependent protective effects in experimental colitis act indirectly on CD4(+)CD62L(+) T cells. While the involvement of B cells could be excluded, CD11c(+) DCs were identified as key mediators of CpG-ODN-induced protection in experimental colitis.
authors: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. claudia.hofmann@klinik.uni-regensburg.de
authors: Claudia
authors: C
authors: Hofmann
authors: Nadja
authors: N
authors: Dunger
authors: Nicole
authors: N
authors: Grunwald
authors: Günter J
authors: GJ
authors: Hämmerling
authors: Petra
authors: P
authors: Hoffmann
authors: Jürgen
authors: J
authors: Schölmerich
authors: Werner
authors: W
authors: Falk
authors: Florian
authors: F
authors: Obermeier
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology / Q000517:prevention & control*; D004269:DNA, Bacterial / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D007370:Interferon Type I / Q000276:immunology; D019041:L-Selectin / Q000032:analysis; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D018941:Antigens, CD19; C408982:CPG-oligonucleotide; D004269:DNA, Bacterial; D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides; D019041:L-Selectin