BACKGROUND Antibody against CD40 is effective in enhancing immune responses to vaccines when chemically conjugated to the vaccine antigen. Unfortunately the requirement for chemical conjugation presents some difficulties in vaccine production and quality control which are compounded when multivalent vaccines are required. We explore here an alternative to chemical conjugation, involving the co-...

Evidence has accumulated that antigen-specific T cells infiltrate the heart and play an important role in the pathogenesis of viral myocarditis. Costimulatory molecules such as B7s and CD40 expressed on antigen-presenting cells are known to play a critical role for antigen-specific T-cell activation to occur. To investigate the role for a costimulatory molecule, CD40, in the development of acut...

Atherogenesis is the consequence of a variety of effector mechanisms rather than the result of a single functional molecule. In this connection, type IIA secretory phospholipase A2 (sPLA2) is an acute-phase reactant, which accumulates in atherosclerotic arterial walls, elicits several effects on monocytes, and has been related to the development of atherosclerosis. CD40/CD40 ligand pair is also...

We and others previously observed that IgM and CD40 stimulation in murine B cells resulted in activation of extracellular signal-regulated kinase (ERK), a subfamily of mitogen-activated protein kinase. The present study demonstrated that ERK was rapidly phosphorylated and translocated to the nucleus in murine B cells upon stimulation with CD40, whereas it was preferentially localized within the...

Recently, it has been demonstrated that the CD40 receptor is constitutively expressed on cultured microglia at low levels. Ligation of CD40 by CD40 ligand on these cells results in microglial activation, as measured by TNF-alpha production and neuronal injury. However, the intracellular events mediating this effect have yet to be investigated. We report that ligation of microglial CD40 triggers...

An elevated number of myeloid-derived suppressor cells (MDSCs) in tumor-bearing hosts has been recognized as a crucial mediator of tumor progression due to the cells potent ability to suppress antitumor immunity. Cluster of differentiation (CD) 40, as a suppressive phenotype expressed in MDSCs, is essential for MDSC-mediated immune suppression and the expansion of T regulatory cells. However, w...

Since CD40/CD40 ligand (CD40Lig) interactions are essential in vivo for the generation of germinal center B cells that express Fas (Apo-1/CD95), we explored whether CD40 engagement may modulate Fas expression and function on human B lymphocytes. Resting tonsil B cells, isolated by density gradient centrifugation, express either absent or low levels of Fas. They could be induced to promptly expr...

The macrophage-expressed CD40 regulates immune responses to Leishmania major infection by reciprocal signaling through p38 MAPK and ERK1/2. CD40-induced IL-10 or IL-12 plays crucial roles in the promotion or protection from L. major infection, respectively. Because p38 MAPK and ERK1/2 are dephosphorylated by dual-specificity MAPK phosphatases (MKPs), we tested the role of CD40 in the regulation...

EBV-encoded latent membrane protein 1 (LMP1) is critical for EBV-driven B-cell transformation and most EBV-associated malignancies and is also implicated in exacerbation of autoimmunity. LMP1 functionally mimics the TNFR superfamily member CD40, but LMP1-induced signals and downstream B-cell functions are amplified and sustained compared with those mediated by CD40. CD40 and LMP1 both depend up...