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.

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.

• Authors: Claudia Hofmann, Nadja Dunger, Nicole Grunwald, Günter J Hämmerling, Petra Hoffmann, Jürgen Schölmerich, Werner Falk, Florian Obermeier
• Journal: Gut (Gut) Vol. 59 Issue 10 Pg. 1347-54 (Oct 2010) ISSN: 1468-3288 [Electronic] England
• PMID: 20732920 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD19
• CPG-oligonucleotide
• DNA, Bacterial
• Interferon Type I
• Oligodeoxyribonucleotides
• L-Selectin

Topics

• Animals
• Antigens, CD19 (analysis)
• B-Lymphocyte Subsets (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Coculture Techniques
• Colitis (immunology, prevention & control)
• DNA, Bacterial (immunology)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Interferon Type I (immunology)
• L-Selectin (analysis)
• Lymphocyte Transfusion
• Mice
• Mice, SCID
• Mice, Transgenic
• Oligodeoxyribonucleotides (immunology)
• Spleen (immunology)
• T-Lymphocyte Subsets (immunology)