Induction of antigen-specific regulatory T cells in the liver-draining celiac lymph node following oral antigen administration.

• Regulatory T cells are induced by oral administration of an antigen, but the physiological requirements and localization of the inductive sites are largely unknown. Using an adoptive transfer system of cells transgenic for ovalbumin T-cell receptor (OVA TCR tg), we found that antigen-specific CD4+ T cells were activated in the liver-draining celiac lymph node (CLN) shortly after ovalbumin feeding, and that a significantly higher proportion of the T cells in the CLN developed into the putative regulatory phenotype [co-expressing CD25 with the glucocortico-induced tumour necrosis factor (TNF) receptor family related gene (GITR), cytotoxic T-lymphocyte antigen (CTLA)-4 and CD103] than in Peyer's patches, the mesenteric and peripheral lymph nodes and the spleen. In addition, a particularly high level of expression of CD103 on the OVA-specific T cells in the CLN may favour homing to the epithelium of the intestine. While equally suppressive, OVA tg T cells isolated from the CLN of OVA-fed DO11.10 mice were less dependent on transforming growth factor (TGF)-beta for suppression than cells isolated from the peripheral and mesenteric lymph nodes, which indicates the involvement of an additional suppressive mechanism. The expression of FoxP3 was not up-regulated in any of the lymph node compartments studied. Our phenotypic and functional findings suggest that the induction of regulatory T cells in the CLN may be relevant in the control of the immune response to dietary antigens.

Nyckelord

Administration

Oral

Adoptive Transfer

methods

Animals

Antigens

CD

metabolism

Antigens

Differentiation

metabolism

CD4-Positive T-Lymphocytes

immunology

Celiac Artery

immunology

Epitopes

T-Lymphocyte

immunology

Female

Flow Cytometry

methods

Forkhead Transcription Factors

metabolism

Immune Tolerance

immunology

Immunity

Mucosal

Immunophenotyping

Integrin alpha Chains

metabolism

Intestinal Mucosa

immunology

Liver

immunology

Lymph Nodes

immunology

Lymphocyte Activation

immunology

Male

Mice

Mice

Inbred BALB C

Ovalbumin

immunology

Proteins

immunology

Receptors

Interleukin-2

metabolism

Receptors

Nerve Growth Factor

metabolism

Receptors

Tumor Necrosis Factor

metabolism

T-Lymphocyte Subsets

immunology

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