Impaired regulatory T cell function in germ-free mice

Eur J Immunol. 2006 Sep;36(9):2336-46. doi: 10.1002/eji.200535244.


Regulatory T cells (Treg) are crucial for the maintenance of tolerance to auto-antigens and harmless exogenous antigens. Here, we studied the role of the commensal microbiota for the development and function of Treg. CD4+CD25+ T cells were obtained from peripheral lymph nodes (PLN) and mesenteric lymph nodes (MLN) of germ-free (GF) and conventional (conv) NMRI mice and tested for phenotype and functional suppressive capacity. CD4+CD25+ T cells from GF mice showed a lower relative gene expression of fork head box p3 gene (Foxp3) and were not as potent suppressors in vitro as CD4+CD25+ T cells from conv animals. Intracellular staining for Foxp3 and CTLA-4 revealed proportional and regional differences in putative Treg subsets between conv and GF mice. Fewer of the CD4+CD25+ T cells in GF MLN expressed Foxp3 and CTLA-4, while the expression of these markers was similar amongst the CD4+CD25+ T cells in PLN of conv and GF mice. The largest difference between conv and GF Treg was observed in the liver draining celiac lymph node, where GF mice had fewer putative Treg as compared to conv mice. We propose that the presence of a microbial flora favors the development of a fully functional Treg population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / immunology
  • CD4 Antigens / biosynthesis
  • CD4 Antigens / immunology
  • CTLA-4 Antigen
  • Flow Cytometry
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology
  • Gene Expression
  • Germ-Free Life*
  • Immune Tolerance*
  • Interleukin-10 / biosynthesis
  • Interleukin-13 / biosynthesis
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Phenotype
  • RNA, Messenger / analysis
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • CD4 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-13
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Interleukin-10