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OX40 Ligand (ox40 + ligand)

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Medical Sciences	100%

Selected Abstracts

CD40 and OX40 ligand are differentially regulated on asthmatic airway smooth muscle

ALLERGY, Issue 7 2009
D. I. Krimmer
Background:, CD40 and OX40 Ligand (OX40L) are cell-surface molecules expressed on airway smooth muscle (ASM) that can enhance inflammatory cell activation and survival. The aim of this study was to examine the effect of tumour necrosis factor-alpha (TNF-,) and interferon-gamma (IFN-,) on ASM CD40 and OX40L expression. Methods:, CD40 and OX40L expression on human ASM cells from asthmatic and nonasthmatic donors following stimulation with TNF-, and/or IFN-, was measured using cell-surface enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Involvement of signalling pathway was investigated with pharmacological inhibitors. Soluble TNF receptor levels were quantified by ELISA. Results:, Interferon-, and TNF-, synergistically increased CD40 expression to a greater extent on asthmatic than on nonasthmatic ASM. In contrast, IFN-, reduced TNF-,-induced OX40L expression to a similar extent in both cell types. TNF-, and IFN-, induced CD40 via nuclear factor-,B (NF-,B) and signal transducer and activator of transcription-3 in both cell types and modulated OX40L via NF-,B and c-Jun N terminal kinase in nonasthmatic cells. Similar effects on the induction of OX40L in asthmatic cells were seen with NF-,B, but these were not statistically significant. The reduced OX40L expression with TNF-, and IFN-, involved extracellular regulated kinase 1/2 activation. Conclusion:, Asthmatic ASM may modulate airway inflammation locally by increasing CD40 and OX40L expression in response to cytokines. IFN-, may regulate ASM pro-inflammatory actions by differentially modulating ASM CD40 and OX40L expression. [source]

Expression of gp34 (OX40 Ligand) and OX40 on Human T Cell Clones

CANCER SCIENCE, Issue 4 2001
Naruhiko Takasawa
gp34, which we previously cloned, is a ligand of OX40 (CD 134), a costimulatory molecule involved in T cell activation. To elucidate the role of human OX40/OX40L interaction, we examined the expression of gp34 (OX40L) and OX40 in normal human hematopoietic cells by using flow cytometry. OX40 expression is observed on activated T cells, while OX40L is expressed in antigen-presenting cells. However, cytotoxic T lymphocyte (CTL) clones specific for Epstein-Barr virus (EBV)-transformed autologous lymphoblastic cell lines (LCLs) induced both OX40 and OX40L expression after antigen or T cell receptor (TCR) stimulation. This study suggests a possible function of OX40L/OX40, through T cell-T cell interaction, in the reactivation of memory T cells in an auto-crine manner, with implications for the pathogenesis of viral infections and neoplasms. [source]

Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa

ALLERGY, Issue 8 2010
T. Liu
To cite this article: Liu T, Xie C, Chen X, Zhao F, Liu A-M, Cho D-B, Chong J, Yang P-C. Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa. Allergy 2010; 65: 969,977. Abstract Background:, The prevalence of airway inflammatory disorders keeps rising; its pathogenic mechanism is still not fully understood. Objective:, The present study aimed to investigate the role of muscarinic receptor (M receptor) in regulating the immune cell activity in nasal mucosa by using surgical removed nasal mucosa from patients with nasal polyposis (NP) as a study platform. Methods:, Human nasal mucosal sample was collected from inferior turbinectomy of 86 patients with NP or/and allergic rhinitis. Expression of tumor necrosis factor alpha (TNF-alpha), M receptor, OX40 ligand was measured in nasal mucosa by enzyme-linked immunosorbent assay, flow cytometry, and Western blotting assay. Results:, When compared with non-NP (nNP) nasal mucosa, contents of TNF-alpha and TNF-alpha(+) cells markedly increased in NP nasal mucosa; immune staining colocalized M3 receptor(+) and TNF-alpha(+) cells in NP nasal mucosa; exposure of isolated CD4(+) T cells to methacholine induced the release of TNF-alpha. We also found CD11c(+)/M3 receptor(+) cells in NP nasal mucosa. Methacholine increased the expression of OX40L in dendritic cells. Staphylococcal (S) aureus and S. enterotoxin B (SEB) were detected in NP nasal mucosa. Exposure of dendritic cells or naïve CD4(+) T cells to SEB initiated the expression of M3 receptor at mRNA and protein levels. Conclusions:, The present data demonstrate that parasympathetic activity has the capacity to activate dendritic cells to release OX40 ligand, the latter induces CD4(+) T cells to produce IL-4 and TNF-alpha that may further contribute to the pathogenesis of NP. [source]

CD40 and OX40 ligand are differentially regulated on asthmatic airway smooth muscle

Retroviral transduction of acute myeloid leukaemia-derived dendritic cells with OX40 ligand augments their antigen presenting activity

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004
Soshi Yanagita
Summary Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms -like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF- ,. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8·5,27·2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)- , producing CD4+ T cells and in production of IFN- ,. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells. [source]