Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis

Strouch, U. G.; Obermeier, F.; Grunwald, N.; Gürster, S.; Dunger, N.; Schultz, M.; Griese, D. P.; Mähler, M.; Schölmerich, J.; Rath, H. C.
November 2005
Gut;Nov2005, Vol. 54 Issue 11, p1546
Academic Journal
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+CD62L- lymphocytes 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+CD62L- cells from germ free mice were not able to abrogate colitis induced by cotransfer with CD4+CD62L+ lymphocytes whereas CD4+CD62L- T 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.


Related Articles

  • IL-6 positively regulates Foxp3+CD8+ T cells in vivo. Nakagawa, Takayuki; Tsuruoka, Mineko; Ogura, Hideki; Okuyama, Yuko; Arima, Yasunobu; Hirano, Toshio; Murakami, Masaaki // International Immunology;Feb2010, Vol. 22 Issue 2, p129 

    Although recent studies have identified regulatory roles for Foxp3+CD8+ T cells, the mechanisms that induce their development and underlie their functions in vivo have not been elucidated. Here, we show that IL-6 positively regulates the Foxp3+CD8+ T-cell development and function. The Foxp3+CD8+...

  • Surveillance B lymphocytes and mucosal immunoregulation. Velázquez, Peter; Wei, Bo; Braun, Jonathan // Springer Seminars in Immunopathology;Mar2005, Vol. 26 Issue 4, p453 

    Mucosal lymphocyte homeostasis involves the dynamic interaction of enteric microbiota, the intestinal host epithelium, and the mucosal immune system. Dysregulation of mucosal lymphocyte homeostasis results in a variety of intestinal disorders, notably inflammatory bowel diseases like ulcerative...

  • Multipotential acceptance of Peyer's patches in the intestine for both thymus-derived T cells and extrathymic T cells in mice. Takahashi, Satoshi; Kawamura, Toshihiko; Kanda, Yasuhiro; Taniguchi, Tomoyo; Nishizawa, Tetsuro; Iiai, Tsuneo; Hatakeyama, Katsuyoshi; Abo, Toru // Immunology & Cell Biology;Oct2005, Vol. 83 Issue 5, p504 

    Peyer's patches (PP) are important inductive sites for the mucosal immune response. It is well known that lymphocytes that migrate into PP are mainly of T-cell lineage from thymus-derived cells (i.e. αβTCRhigh cells). In this study, we further characterized the properties of PP lymphocytes...

  • CD4+CD45RBHi T cell transfer induced colitis in mice is accompanied by osteopenia which is treatable with recombinant human osteoprotegerin. Byrne, F. R.; Morony, S.; Warmington, K.; Geng, Z.; Brown, H. L.; Flores, S. A.; Fiorino, M.; Yin, S. L.; Hill, D.; Porkess, V.; Duryea, D.; Pretorius, J. K.; Adamu, S.; Manuokian, R.; Danilenko, D. M.; Sarosi, I.; Locey, D. I.; Kostenuik, P. J.; Senaldi, G. // Gut;Jan2005, Vol. 54 Issue 1, p78 

    Background and aims: Transfer of CD4+CD45RBHi T cells into semi syngeneic immunodeficient mice represents a model of inflammatory bowel disease (IBD). As patients with IBD often suffer from osteopenia, we studied if this T cell transfer in mice results in osteopenia in addition to colitis, and...

  • 111Indium Leucocyte Scanning in Ampicillin-Associated Right- Sided Hemorrhagic Colitis. Keshavarzian, A.; Saverymuttu, S. H.; Chadwick, V. S. // American Journal of Gastroenterology;Jul1984, Vol. 79 Issue 7, p541 

    Hemorrhagic colitis is a rare but well-recognized complication with ampicillin or penicillin derivative treatment. Early colonoscopy has been advocated in establishing the diagnosis by demonstrating the characteristic pattern of only right-sided involvement and so distinguishing it from other...

  • Effects of Antioxidant Therapy on Leukocyte Myeloperoxidase and Cu/Zn-Superoxide Dismutase and Plasma Malondialdehyde Levels in Experimental Colitis. Kurutas, Ergul Beige; Cetinkaya, Ali; Bulbulogiu, Ertan; Kantarceken, Bulent // Mediators of Inflammation;12/14/2005, Vol. 2005 Issue 6, p390 

    The aim of the present study was to evaluate the effects of N-acetylcysteine (NAC) and L-carnitine (LCAR) supplementations on polymorphonuclear leukocytes myeloperoxidase (MPO) and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and plasma malondialdehyde (MDA) in acetic acid (AA)-induced ulcerative...

  • Neutrophil elastase in colitis: more than a marker of disease activity? Hokari, Ryota; Miura, Soichiro // Journal of Gastroenterology;Apr2006, Vol. 41 Issue 4, p395 

    The article reports on neutrophil elastase in colitis. Neutrophil elastase (NE) plays a major role in tissue destruction through its protease activity and is a major secretory product from activated neutrophils. It also has many biological functions through its activation of cell surface...

  • Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis. Morohoshi, Yuichi; Matsuoka, Katsuyoshi; Chinen, Hiroshi; Kamada, Nobuhiko; Sato, Toshiro; Hisamatsu, Tadakazu; Okamoto, Susumu; Inoue, Nagamu; Takaishi, Hiromasa; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi // Journal of Gastroenterology;Apr2006, Vol. 41 Issue 4, p318 

    Background. Neutrophil elastase (NE) is a major secretory product from activated neutrophils and a major contributor to tissue destruction. However, little is known about the pathogenic contribution of NE to ulcerative colitis (UC). This study was designed to investigate the contribution of NE...

  • Use of Budesonide in the Treatment of Microscopic Colitis. Tangri, Vikram; Chande, Nilesh // Saudi Journal of Gastroenterology;Jul2010, Vol. 16 Issue 3, p236 

    Collagenous colitis and lymphocytic colitis, the two types of microscopic colitis, cause watery diarrhea. Budesonide, a glucocorticoid medication with limited systemic availability, is commonly used to treat these illnesses. Budesonide has proven efficacy in the induction of clinical remission...


Read the Article


Sign out of this library

Other Topics