How is a dendritic cell licensed?
DCs provide both signals when activated by ligands of pattern recognition receptors and “licensed” by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (“classical licensing”) or by natural killer T cells (“alternative licensing”).
What is CD40 a marker for?
In mice levels of CD40 are used as a marker to distinguish between inactivated and activated DCs, as its expression is up-regulated on DCs after encounter with microbial products (e.g. Toll-like receptor ligands) [40] and pathogens (e.g. viruses like HIV), as well as after uptake of apoptotic cells [41].
What is anti CD40?
A proprietary, non-fucosylated monoclonal antibody directed against the cell surface receptor CD40 with potential immunostimulatory and antineoplastic activities.
Do all B cells express CD40?
However, while CD40L is expressed on a range of cell types including activated T cells and B cells, dendritic cells granulocytes, macrophages and platelets, only CD40L on T cells is considered by most immunologists when planning experiments or analysing data.
What does CD40 agonist do?
Agonistic CD40 antibodies have been shown to substitute for T cell help provided by CD4+ lymphocytes in murine models of T cell-mediated immunity. In tumor-bearing hosts, CD40 agonists trigger effective immune responses against tumor-associated antigens.
What is a CD40 agonist?
CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma.
What is the function of CD40L?
The ligand for CD40, CD154 (also known as TRAP, T-BAM, CD40 Ligand or CD40L) is a 34–39 kilodalton type II integral membrane protein. Initially CD40L was reported to be expressed principally on activated CD4+T cells, which led to models that the main function of CD40L was to provide T cell help to B cells [25].
Does CD40 Express in macrophage?
In addition, CD40 also expresses in the macrophage and B cells. In macrophage, the primary signal for activation is IFN-γ from Th1 type CD4+T cells. The secondary signal is CD40L on the T cell which binds CD40 on the macrophage cell surface.
Why is CD40 upregulated in activated T cells?
CD40 is upregulated on activated DCs and CD40L is expressed on activated T cells. Engagement of CD40 on DCs induces positive signaling that leads to expression of CD80/86 and the production of IL-12 that skews towards Th1 differentiation in CD4+T cells. In addition to IL-12, CD40L signaling in T cells induces IFN-γ production.
How do different cell types respond to CD40 crosslinking?
Although DCs resembled B cells in these responses to CD40 crosslinking [ 9 ], it soon became apparent that different cell types respond in distinct ways to CD40 stimulation; for instance, while CD40 ligation promotes B cells to survive, it promotes some epithelial to die [ 21] and others to produce GM-CSF [ 22 ].