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T cell-dependent protective effects of CpG motifs of bacterial DNA in experimental colitis are mediated by CD11c+ dendritic cells
  1. Claudia Hofmann1,
  2. Nadja Dunger1,
  3. Nicole Grunwald1,
  4. Günter J Hämmerling2,
  5. Petra Hoffmann3,
  6. Jürgen Schölmerich1,
  7. Werner Falk1,
  8. Florian Obermeier1
  1. 1Department of Internal Medicine I, Regensburg University Medical Center, Germany
  2. 2Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany
  3. 3Department of Hematology and Oncology, Regensburg University Medical Center, Germany
  1. Correspondence to Claudia Hofmann, Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany; claudia.hofmann{at}klinik.uni-regensburg.de

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.

Aims 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.

  • Dendritic cells
  • experimental colitis
  • TLR9
  • CpG
  • IBD basic research
  • mucosal immunology
  • Revised 29 March 2010
  • Accepted 15 June 2010

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Footnotes

  • Funding This work was supported by a DFG grant to FO (OB 135/10-2).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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