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The immune response in the gastrointestinal tract is a tightly controlled balance between effector and regulatory cell responses. Here, we have investigated the role of OX40 in influencing the balance between conventional T cells and Foxp3+ regulatory T (T reg) cells. Under steady-state conditions, OX40 was required by T reg cells for their accumulation in the colon, but not peripheral lymphoid organs. Strikingly, under inflammatory conditions OX40 played an essential role in T reg cell-mediated suppression of colitis. OX40(-/-) T reg cells showed reduced accumulation in the colon and peripheral lymphoid organs, resulting in their inability to keep pace with the effector response. In the absence of OX40 signaling, T reg cells underwent enhanced activation-induced cell death, indicating that OX40 delivers an important survival signal to T reg cells after activation. As OX40 also promoted the colitogenic Th1 response, its expression on T reg cells may be required for effective competition with OX40-dependent effector responses. These results newly identify a key role for OX40 in the homeostasis of intestinal Foxp3+ T reg cells and in suppression of colitis. These fi ndings should be taken into account when considering OX40 blockade for treatment of IBD.

Original publication

DOI

10.1084/jem.20091618

Type

Journal article

Journal

J Exp Med

Publication Date

12/04/2010

Volume

207

Pages

699 - 709

Keywords

Animals, Antigens, CD45, Apoptosis, CD4-Positive T-Lymphocytes, Cell Count, Cell Movement, Cell Proliferation, Colitis, Colon, Disease Models, Animal, Forkhead Transcription Factors, Gene Expression, Homeodomain Proteins, Integrins, Interferon-gamma, Interleukin-17, Intestinal Mucosa, Lymphocyte Activation, Lymphoid Tissue, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Receptors, OX40, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Tumor Necrosis Factors