Article Text

Download PDFPDF
Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis
  1. U G Strauch1,
  2. F Obermeier1,
  3. N Grunwald1,
  4. S Gürster1,
  5. N Dunger1,
  6. M Schultz1,
  7. D P Griese2,
  8. M Mähler3,
  9. J Schölmerich1,
  10. H C Rath1
  1. 1Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
  2. 2Department of Internal Medicine II, University of Regensburg, Regensburg, Germany
  3. 3Institute for Laboratory Animal Science and Central Animal Facility, Medical School Hannover, Hannover, Germany
  1. Correspondence to:
    Dr U G Strauch
    Department of Internal Medicine I, University of Regensburg, D-93053 Regensburg, Germany;


Background: The resident flora plays a critical role in initiation and perpetuation of intestinal inflammation, as demonstrated in experimental models of colitis where animals fail to develop disease under germ free conditions. However, the importance of exposure to commensal bacteria before the onset of colitis is unclear. Our aim was to investigate the influence of previous exposure of donor animals to bacterial antigens on colitis development using a transfer model.

Methods: Clinical course and histology were evaluated after transfer of CD4+CD62L+ lymphocytes from germ free and conventionally housed donor mice into SCID recipients. Cotransfer of CD4+CD62L+ cells with CD4+CD62Llymphocytes from both groups of mice was initiated. Lymphocytes were analysed by FACS, polarisation potential of cells determined, and cytokines measured within the supernatant by enzyme linked immunosorbent assay.

Results: Animals that received cells from germ free donors developed an earlier onset of colitis compared with mice reconstituted with lymphocytes from conventionally housed animals. Additionally, CD4+CD62Lcells from germ free mice were not able to abrogate colitis induced by cotransfer with CD4+CD62L+ lymphocytes whereas CD4+CD62LT cells from normal mice ameliorated disease. The higher percentage of CD4+GITR+ expressing lymphocytes and the production of interleukin 10 after priming by dendritic cells suggests the presence of Treg cells within the CD4+CD62L+ lymphocyte subset derived from conventional housed mice and assumes a lack of Treg cells within germ free mice.

Conclusion: The results indicate that bacterial antigens are crucial for the generation and/or expansion of Treg cells in a healthy individual. Therefore, bacterial colonisation is of great importance in maintaining the immunological balance.

  • IBD, inflammatory bowel disease
  • GF, germ free
  • BM-DC, bone marrow derived dendritic cells
  • MLN, mesenteric lymph node
  • GITR, glucocorticoid induced tumour necrosis factor receptor related protein
  • TNF-α, tumour necrosis factor α
  • IL, interleukin
  • IFN-γ, interferon γ
  • mAbs, monoclonal antibodies
  • ELISA, enzyme linked immunosorbent assay
  • TGF-β1, transforming growth factor β1
  • RT-PCR, reverse transcription-polymerase chain reaction
  • inflammatory bowel disease
  • intestinal bacteria
  • germ free mice
  • regulatory T cells
  • colitis
  • adoptive transfer model

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published online first 29 June 2005

  • Conflict of interest: None declared.