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*
Department of Paediatric Gastroenterology, St. Bartholomew’s and The Royal London School of Medicine and Dentistry, St. Bartholomew’s Hospital, London, United Kingdom; and
Cantab Pharmaceuticals Limited, Cambridge, United Kingdom
OX40 is a member of the TNFR superfamily, and is found
predominantly on activated CD4-positive T cells. In vitro an OX40-IgG
fusion protein inhibits mitogen- and Ag-driven proliferation and
cytokine release by splenocytes and lymph node T cells. In contrast, an
OX40 ligand-IgG fusion protein enhanced proliferative responses. In
normal mice, OX40-positive cells are observed only in lymphoid tissues,
including Peyer’s patches of the gut. In mice with hapten-induced
colitis or IL-2 knockout mice with spontaneous colitis, OX40-positive
cells are found infiltrating the lamina propria. Administration of the
OX40-IgG fusion protein to mice with ongoing colitis (but not the OX40
ligand-IgG) ameliorated disease in both mouse models of inflammatory
bowel disease. This was evidenced by a reduction in tissue
myeloperoxidase; reduced transcripts for TNF-
, IL-1, IL-12, and
IFN-
; and a reduction in the T cell infiltrate. Targeting OX40
therefore shows considerable promise as a new strategy to inhibit
ongoing T cell reactions in the gut.
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H. Akiba, Y. Miyahira, M. Atsuta, K. Takeda, C. Nohara, T. Futagawa, H. Matsuda, T. Aoki, H. Yagita, and K. Okumura Critical Contribution of OX40 Ligand to T Helper Cell Type 2 Differentiation in Experimental Leishmaniasis J. Exp. Med., January 17, 2000; 191(2): 375 - 380. [Abstract] [Full Text] [PDF]
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H S Souza, C C S Elia, J Spencer, and T T MacDonald Expression of lymphocyte-endothelial receptor-ligand pairs, alpha 4beta 7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease Gut, December 1, 1999; 45(6): 856 - 863. [Abstract] [Full Text] [PDF]
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