Allorejection and recurrence of autoimmunity are the major barriers to transplantation of islets of Langerhans for the cure of type 1 diabetes in humans. CD40-CD154 (CD40 ligand) interaction blockade by the use of anti-CD154 monoclonal antibody (mAb) has shown efficacy in preventing allorejection in several models of organ and cell transplantation. Here we report the beneficial effect of the ch...

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...

CD154 (CD40 ligand, CD40L, gp139) is a co-stimulatory molecule of the tumour necrosis factor (TNF) family. CD154 was originally discovered on T-cells, and was found to be involved in many immune responses including B-cell activation, isotype switching, and germinal centre formation. The expression of CD154 on other haematopoietic and non-haematopoietic cells suggests that CD154 has other functi...

BACKGROUND Hypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. ME...

CD154 (CD40 ligand) expression on CD4 T cells is normally tightly controlled, but abnormal or dysregulated expression of CD154 has been well documented in autoimmune diseases, such as systemic lupus erythematosus. Beyond regulation by NFAT proteins, little is known about the transcriptional activation of the CD154 promoter. We identified a species-conserved purine-rich sequence located adjacent...

BACKGROUND CD154/CD40 interactions play a pivotal role both in humoral and cellular immune responses. Their involvement in the pathogenesis of chronic inflammatory bowel disease (IBD) has been revealed by increased expression of CD40 and CD154 in the inflamed mucosa of patients and the therapeutic effects of anti-CD154 antibodies in experimental colitis. Because of adverse side effects however,...

The CD40-CD154 interaction is better exemplified by a rheostat than by an on-off switch, and variations in its intensity can play a role in the regulation of B lymphocyte activation following primary and/or secondary humoral immune response. The CD40-CD154 interaction is often studied in co-culture models using CD154+ adherent cells, which can be problematic when performing protein or gene anal...

Abnormalities in B-lymphocyte CD40 ligand (CD154) expression have been described for a number of immunologic diseases, including B-cell lymphomas. Although functional analysis of the CD154 gene and protein has been extensive, little is known about the mechanisms controlling CD154 expression in activated T cells, and even less is known for normal and malignant B cells. In this study we describe ...