Totsuka, T., T. Kanai, K. Uraushihara, R. Iiyama, M. Yamazaki, H. Akiba, H. Yagita, K. Okumura, and M. Watanabe. Therapeutic effect of anti-OX40L and antiTNFMAbs in a murine model of chronic colitis. Am J Physiol Gastrointest Liver Physiol 284: G595–G603, 2003. First published January 10, 2003; 10.1152/ajpgi.00450. 2002.—Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-...

Dendritic cells (DCs) show a functional plasticity in determining Th responses depending on their maturational stage or on maturational signals delivered to the DCs. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively. In this study we have investigated the Th-polarizing capacity of PDCs after short (24-h) or long (72-...

IL-10-producing CD4(+) type 1 regulatory T (Tr1) cells play a critical role in the maintenance of peripheral tolerance. Although immunosuppressive drugs, cytokines, costimulatory molecules, and immature dendritic cells are implicated in the induction of Tr1 cells, the signals that negatively regulate the generation and function of Tr1 cells have been elusive. We report that OX40 ligand (OX40L) ...

The human breast tumor microenvironment can display features of T helper type 2 (Th2) inflammation, and Th2 inflammation can promote tumor development. However, the molecular and cellular mechanisms contributing to Th2 inflammation in breast tumors remain unclear. Here, we show that human breast cancer cells produce thymic stromal lymphopoietin (TSLP). Breast tumor supernatants, in a TSLP-depen...

BACKGROUND The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells. OBJECTIVE We tested whether treatment with an anti-OX40L monoclonal antibody (MAb) would inhibit allergen-induced responses in subjects with asthma. METHODS Twenty-eight mild, atopic asthmatic s...

Signals through the OX40 costimulatory receptor on naive CD4 T cells are essential for full-fledged CD4 T cell activation and the generation of CD4 memory T cells. Because the ligand for OX40 is mainly expressed by APCs, including activated B cells, dendritic cells, and Langerhans cells, the OX40-OX40 ligand (OX40L) interaction has been thought to participate in T cell-APC interactions. Althoug...

Influenza virus epidemics potentially cause pneumonia, which is responsible for much of the mortality due to the excessive immune responses. The role of costimulatory OX40-OX40 ligand (OX40L) interactions has been explored in the non-infectious pathology of influenza pneumonia. Here, we describe a critical contribution of OX40L to infectious pathology, with OX40L deficiency, but not OX40 defici...

The OX40 receptor is preferentially expressed by T cells, and its cognate ligand OX40L is primarily expressed by antigen-presenting cells such as dendritic cells following activation by thymic stromal lymphopoietin (TSLP). TSLP is released by the bronchial epithelium, airway smooth muscle, and some inflammatory cells in response to numerous insults such as allergens, viruses, and physical damag...

PURPOSE We tested the combination of a tumor lysate vaccine with a panel of costimulatory molecules to identify an immunotherapeutic approach capable of curing established murine gliomas. EXPERIMENTAL DESIGN Glioma-bearing mice were primed with a tumor lysate vaccine, followed by systemic administration of the following costimulatory ligands: OX40L, CD80, 4-1BBL, and GITRL, which were fused t...

Costimulatory cross-talk can occur at multiple cellular levels to potentiate expansion and polarization of Th responses. Although OX40L ligand (OX40L) is thought to play a key role in Th2 development, the critical cellular source of this molecule has yet to be identified. In this study, we demonstrate that OX40L expression by the initiating dendritic cell (DC) is a fundamental requirement for o...