Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

The Journal of Experimental Medicine

Publication Date

05/04/2010

Volume

207

Pages

699 - 709

Addresses

Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, England, UK.

Keywords

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