CD40L, or CD154, is canonically expressed on CD4+ T cells and it is a principal modulator of a wide range of humoral and cellular immune responses (1, 2). One of the primary functions of CD40L is the T cell-mediated activation of DCs and monocytes (3, 4), in a process known as DC licensing.

What is the role of CD40L?

CD40L mediates a range of activities on B cells, including induction of activation-associated surface antigen, entry into cell cycle, isotype switching, Ig secretion, and memory generation. CD40–CD40L interaction also plays important roles in monocyte activation and DC maturation.

Do naive T cells express CD40L?

Under resting conditions, naive CD4 T cells are demonstrated to express CD40L, whereas CD25+ CD4 T cells express lower amounts, and CD8 T cells show minimal expression of this membrane-bound cytokine.

What is the outcome of the interaction between CD40L expressed on CD4 T cells and CD40 expressed on DCs )?

CD40L/CD40 expression is known to be up-regulated in atheroma-associated cells. CD40L/CD40 interactions activate these cells by promoting the expression of molecules thought to be involved in atherosclerotic plaque formation, such as adhesion molecules, cytokines, matrix metalloproteinases, and tissue factor.

Why does a patient with CD40L deficiency have no germinal centers within the lymph node 2 )?

Lymph nodes of patients with CD40L deficiency lack germinal centers, attributed to ineffective CD40L/CD40 interaction in the extrafollicular areas, resulting in poor recruitment of germinal center precursors (21).

Do B cells express CD40L?

CD40L is expressed primarily by activated T cells, as well as activated B cells and platelets; and under inflammatory conditions is also induced on monocytic cells, natural killer cells, mast cells, and basophils (13).

How does CD154 work?

CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper cells (TFH cells). On TFH cells, CD154 promotes B cell maturation and function by engaging CD40 on the B cell surface and therefore facilitating cell-cell communication.

What is CD40L a marker of?

CD40L is a costimulatory molecule and an early activation marker of T-lymphocytes.

What are activated T cells?

T cells are generated in the Thymus and are programmed to be specific for one particular foreign particle (antigen). Once they leave the thymus, they circulate throughout the body until they recognise their antigen on the surface of antigen presenting cells (APCs).

What does it take to activate the cell that activates the T cell?

Helper T cells become activated by interacting with antigen-presenting cells, such as macrophages. Antigen-presenting cells ingest a microbe, partially degrade it, and export fragments of the microbe—i.e., antigens—to the cell surface, where they are presented in association with class II MHC molecules.

Where is CCR7 found?

lymphoid tissues CCR7 Chemokine Receptor CCR7 is expressed in various lymphoid tissues including B and T lymphocytes and mature dendritic cells (DC).

What does ox40 mean?

OX40 ligand

tumor necrosis factor (ligand) superfamily, member 4 (tax-transcriptionally activated glycoprotein 1, 34kDa)
Identifiers
Symbol TNFSF4
Alt. symbols TXGP1, OX-40L, gp34, CD252
NCBI gene 7292

What is the main role of CD40 activation in B cells?

CD40 activation of B cells results in the activation of numerous biochemical pathways, contributing to biological outcomes including enhanced cell survival and proliferation, germinal center formation, memory B cell development, and Ig isotype switching and affinity maturation (2).

Which types of cells are impacted in CD40L deficiency?

CD40L Deficiency The inability of mutated CD40L protein to bind to CD40 affects CD4 T-cell and B-cell interactions, impairing CSR, SHM, T-cell co-stimulation, and development of memory B cells, resulting in a combined immunodeficiency.

What causes CD40 ligand deficiency?

CD40 ligand (CD40L) deficiency or X-linked Hyper-IgM syndrome is a severe primary immunodeficiency caused by mutations in the CD40L gene. Despite currently available treatments, CD40L-deficient patients remain susceptible to life-threatening infections and have poor long term survival.

What causes low IgM levels?

Other causes of decreased levels of serum IgM (i.e., secondary IgM deficiency) are episodes of infection, thymic hypoplasia, celiac disease, autoimmune disease, and certain adult malignancies; and other PIDs (Wiskott-Aldrich syndrome, DOCK8 deficiency, ataxia-telangiectasia, CVID, and XLA, in combination with IgG and …

What cells express CD20?

CD20 (cluster of differentiate 20) is a protein that is expressed on the surface of B cells, starting at the pre-B cell stage and also on mature B cells in the bone marrow and in the periphery.

Where is germinal center?

Germinal centers develop in the B cell follicles of secondary lymphoid tissues during T cell-dependent (TD) antibody responses. The B cells that give rise to germinal centers initially have to be activated outside follicles, in the T cell-rich zones in association with interdigitating cells and T cell help.

Where does affinity maturation occur?

Affinity maturation primarily occurs on surface immunoglobulin of germinal center B cells and as a direct result of somatic hypermutation (SHM) and selection by TFH cells.

What produces CTLA4?

Function. CTLA4 is a member of the immunoglobulin superfamily that is expressed by activated T cells and transmits an inhibitory signal to T cells.

What does IL 2 Do to T cells?

IL-2 plays a dual role in T cell activation by stimulating the proliferation and differentiation of ‘conventional’ T cells as well as maintaining and expanding the population of ‘suppressive’ Treg cells (Fig. 2)11.

What is CD80 and CD86?

CD80 (B7-1) and CD86 (B7-2) are functionally equivalent in the initiation and maintenance of CD4+ T-cell proliferation after activation with suboptimal doses of PHA. DNA Cell Biol.

How does B cells get activated?

B cells are activated when their B cell receptor (BCR) binds to either soluble or membrane bound antigen. This activates the BCR to form microclusters and trigger downstream signalling cascades. … Cytokines produced by T cells and other cells are important in determining what isotype the B cells express.

Do all T cells have CD3?

CD3 is initially expressed in the cytoplasm of pro-thymocytes, the stem cells from which T-cells arise in the thymus. … The antigen is found bound to the membranes of all mature T-cells, and in virtually no other cell type, although it does appear to be present in small amounts in Purkinje cells.

Is CD40 a costimulation?

Cluster of differentiation 40, CD40 (also known TNFRSF5, Tumor necrosis factor receptor superfamily member 5.) is a costimulatory protein and expresses on antigen presenting cells (APC). In human, CD40 is coded by TNFRSF5 gene and has 7 transcripts.

What are the 3 signals for T cell activation?

Primary T cell activation involves the integration of three distinct signals delivered in sequence: (1) anti- gen recognition, (2) costimulation, and (3) cytokine- mediated differentiation and expansion.

What do suppressor T cells do?

A type of immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. Also called regulatory T cell, T reg, and T-regulatory cell. …

How do you stimulate T cells?

T cells can be activated and differentiated in vitro by crosslinking the TCR with CD3 antibodies and PMA treatment. Additionally, CD28 can be triggered by antibodies directed against it, mimicking APC stimulation.