BACKGROUND Tumor cells in chronic lymphocytic leukemia accumulate in the periphery through the proliferation of a minority of cells in lymph nodes. The proliferative and survival signals in these proliferation centers include interactions with T lymphocytes expressing CD40 ligand. We have demonstrated that the low toxicity combination of bezafibrate and medroxyprogesterone acetate induces mitoc...

Blockade of CD40-CD154 interactions can facilitate long-term allograft acceptance in selected rodent and in primate models, but, due to the ability of CD154-independent CD8(+) T cells to initiate graft rejection, this strategy is not always effective. In this work we demonstrate that blockade of the CD40-CD154 pathway at the time of transplantation enables the generation of donor alloantigen-sp...

OBJECTIVE The CD40/CD40 ligand pathway mediates inflammatory processes important in atherogenesis and the formation of the intraplaque lipid pool. We tested the hypothesis that plasma levels of soluble CD40 ligand are elevated in patients with evidence of a lipid pool on high-resolution magnetic resonance imaging (MRI) of carotid stenoses. METHODS AND RESULTS We recruited 49 patients with evi...

B cells, after mutating their Ig B-region genes in germinal centres (GC), undergo apoptosis, unless they receive antigen-dependent selection signals. The signals appear to be delivered by GC T cells, require CD40 ligand expression and may induce differentiation to memory cells. Cultured GC B cells are prevented from entering apoptosis by ligating their surface CD40, but the resulting phenotype ...

Whereas CD40-CD40 ligand interactions are important for various dendritic cell (DC) functions in vitro, their in vivo relevance is unknown. We analyzed the DC status of CD40 ligand -/- mice using a contact hypersensitivity (CHS) model system that enables multiple functions of DCs to be assessed in vivo. Immunohistochemistry of skin sections revealed no differences in terms of numbers and morpho...

We have shown previously that dendritic cells (DC) produce IL-12 upon interaction with CD4+ T cells. Here we ask how this IL-12 production is induced and regulated. Quantitative PCR and in situ hybridization for IL-12 p40 and an ELISA specific for the p70 heterodimer were used to determine IL-12 production. We demonstrate that ligation of either CD40 or MHC class II molecules independently trig...

CD40 is a molecule present on B lymphocyte lineage cells that is important in B-cell differentiation and activation. Signaling through CD40 has been shown to exert costimulatory signals on normal B cells resulting in proliferative and differentiation responses. Examination of several B-cell lymphomas showed cell-surface expression of the CD40 molecule. Incubation of these lymphomas with anti-CD...

We have reported previously that activation of human umbilical vein endothelial cells (HUVECs) through CD40, using a recombinant soluble form of trimerized CD40 ligand, leads to induction of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). Here, we compare the effects of CD40 ligand with those of tumor necrosis factor (TNF) and interleukin ...

We have reported previously that activation of human umbilical vein endothelial cells (HUVECs) through CD40, using a recombinant soluble form oftrimerized CD40 ligand, leads to induction of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). Here, we compare the effects of CD40 ligand with those of tumor necrosis factor (TNF) and interleukin 1...

CD40 is present on B cells, monocytes, dendritic cells, and endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to assess the effects of a recombinant soluble human CD40 ligand ...