Impaired regulatory T cell function in germ-free mice.

• 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.

Nyckelord

Animals

Antigens

CD

Antigens

CD4

biosynthesis

immunology

Antigens

Differentiation

biosynthesis

immunology

Flow Cytometry

Forkhead Transcription Factors

biosynthesis

immunology

Gene Expression

Germ-Free Life

Immune Tolerance

Interleukin-10

biosynthesis

Interleukin-13

biosynthesis

Lymph Nodes

cytology

immunology

Mice

Phenotype

RNA

Messenger

analysis

Receptors

Interleukin-2

biosynthesis

immunology

T-Lymphocyte Subsets

immunology

T-Lymphocytes

Regulatory

immunology

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