Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (683 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to cd40 antigens on b-lymphocytes and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of hyper-igm immunodeficiency syndrome, TYPE 1.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: T-B Cell Activating Molecule; TNF Superfamily, Member 5; Tumor Necrosis Factor Ligand Superfamily Member 5; CD154 Antigens; gp39 Antigen, T-Cell; gp39 Antigen, T Cell; T-Cell gp39 Antigen; CD40L.
Where it fits in the MeSH classification
- Broader topics
- Membrane Glycoproteins; Tumor Necrosis Factors
- See also
- CD40 Antigens
Related concepts
- Cd40 Antigens
- B-Lymphocytes
- Hyper-Igm Immunodeficiency Syndrome
Research landscape
PubMed indexes 5,867 records tagged with the MeSH heading “CD40 Ligand” (counts retrieved 2026-10-31). 603 of them (10.3%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 2,782 records.
Reviews account for 500 records (8.5%) and meta-analyses for 6. Randomized controlled trials number 122 (2.1%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 803 |
| 2000-2009 | 2,782 |
| 2010-2019 | 1,679 |
| 2020 onward | 603 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 500 | 8.5% |
| Meta-analyses | 6 | 0.1% |
| Randomized controlled trials | 122 | 2.1% |
Method: PubMed query "CD40 Ligand"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Platelets as Key Factors in Inflammation: Focus on CD40L/CD40 | 2022 | Review article Design not recorded in structured metadata | 133 | cc by PMID 35185916 · DOI · PMC8850464 |
| B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses | 2018 | Research article Design not recorded in structured metadata | 87 | cc by PMID 29975708 · DOI · PMC6033398 |
| Composition and structure of synaptic ectosomes exporting antigen receptor linked to functional CD40 ligand from helper T cells | 2019 | Research article Design not recorded in structured metadata | 84 | cc by PMID 31469364 · DOI · PMC6748831 |
| Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy | 2026 | Review article Design not recorded in structured metadata | 0 | cc by PMID 42123447 · DOI · PMC13163484 |
Platelets as Key Factors in Inflammation: Focus on CD40L/CD40 [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Platelets are anucleate cytoplasmic fragments derived from the fragmentation of medullary megakaryocytes.
- Closing excerpt
- As a general rule, all of the studies presented in this review show that platelets are capable of covering most of the stages of inflammation, primarily through the CD40L/CD40 interaction, thus confirming their own role in this pathophysiological condition.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (181 words)
Platelets are anucleate cytoplasmic fragments derived from the fragmentation of medullary megakaryocytes. Activated platelets adhere to the damaged endothelium by means of glycoproteins on their surface, forming the platelet plug. Activated platelets can also secrete the contents of their granules, notably the growth factors contained in the α-granules, which are involved in platelet aggregation and maintain endothelial activation, but also contribute to vascular repair and angiogenesis. Platelets also have a major inflammatory and immune function in antibacterial defence, essentially through their Toll-like Receptors (TLRs) and Sialic acid-binding immunoglobulin-type lectin (SIGLEC). Platelet activation also contributes to the extensive release of anti- or pro-inflammatory mediators such as IL-1β, RANTES (Regulated on Activation, Normal T Expressed and Secreted) or CD154, also known as the CD40-ligand. Platelets are involved in the direct activation of immune cells, polynuclear neutrophils (PNNs) and dendritic cells via the CD40L/CD40 complex. As a general rule, all of the studies presented in this review show that platelets are capable of covering most of the stages of inflammation, primarily through the CD40L/CD40 interaction, thus confirming their own role in this pathophysiological condition.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35185916 · DOI · PMC8850464
B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses.
- Closing excerpt
- In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (249 words)
Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tumoral role but can also be modulated to function as antigen presenting cells to T lymphocytes, capable of triggering anti-cancer immune responses. While dendritic cells, DCs, are the best APC population to activate naive T cells, DCs or their precursors, monocytes, are frequently modulated by tumors, displaying a tolerogenic phenotype in cancer patients. In patients with cervical cancer, we observed that monocyte derived DCs are tolerogenic, inhibiting allogeneic T cell activation compared to the same population obtained from patients with precursor lesions or cervicitis. In this work, we show that B lymphocytes from cervical cancer patients respond to treatment with sCD40L and IL-4 by increasing the CD80+CD86+ population, therefore potentially increasing their ability to activate T cells. To test if B lymphocytes could actually trigger anti-tumor T cell responses, we designed an experimental model where we harvested T and B lymphocytes, or dendritic cells, from tumor bearing donors, and after APC stimulation, transplanted them, together with T cells into RAG1-/- recipients, previously injected with tumor cells. We were able to show that anti-CD40 activated B lymphocytes could trigger secondary T cell responses, dependent on MHC-II expression. Moreover, we showed that dendritic cells were resistant to the anti-CD40 treatment and unable to stimulate anti-tumor responses. In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29975708 · DOI · PMC6033398
Composition and structure of synaptic ectosomes exporting antigen receptor linked to functional CD40 ligand from helper T cells [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Planar supported lipid bilayers (PSLB) presenting T cell receptor (TCR) ligands and ICAM-1 induce budding of extracellular microvesicles enriched in functional TCR, defined here as synaptic ectosomes (SE), from helper T cells.
- Closing excerpt
- CD40L+ SE retain the capacity to induce dendritic cell maturation and cytokine production.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Planar supported lipid bilayers (PSLB) presenting T cell receptor (TCR) ligands and ICAM-1 induce budding of extracellular microvesicles enriched in functional TCR, defined here as synaptic ectosomes (SE), from helper T cells. SE bind peptide-MHC directly exporting TCR into the synaptic cleft, but incorporation of other effectors is unknown. Here, we utilized bead supported lipid bilayers (BSLB) to capture SE from single immunological synapses (IS), determined SE composition by immunofluorescence flow cytometry and enriched SE for proteomic analysis by particle sorting. We demonstrate selective enrichment of CD40L and ICOS in SE in response to addition of CD40 and ICOSL, respectively, to SLB presenting TCR ligands and ICAM-1. SE are enriched in tetraspanins, BST-2, TCR signaling and ESCRT proteins. Super-resolution microscopy demonstrated that CD40L is present in microclusters within CD81 defined SE that are spatially segregated from TCR/ICOS/BST-2. CD40L+ SE retain the capacity to induce dendritic cell maturation and cytokine production.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31469364 · DOI · PMC6748831
Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Diabetic retinopathy is one of the most important complications of diabetes.
- Closing excerpt
- Here we review the role of CD40 as an upstream inducer of these abnormalities and the development of diabetic retinopathy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (103 words)
Diabetic retinopathy is one of the most important complications of diabetes. It is a leading cause of visual loss in the world. While adequate control of hyperglycemia, hypertension and hyperlipidemia can decrease the prevalence of diabetic retinopathy, 60% of patients with type 2 diabetes develop this complication whereas it is estimated that most patients with type 1 diabetes will develop diabetic retinopathy. Upregulation of various pro-inflammatory molecules and vascular endothelial growth factor (VEGF) play a central role in the pathogenesis of the disease. Here we review the role of CD40 as an upstream inducer of these abnormalities and the development of diabetic retinopathy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42123447 · DOI · PMC13163484
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Molecular mechanism and function of CD40/CD40L engagement in the immune system [5]
- Research article The CD40/CD154 receptor/ligand dyad [6]
- Research article CD40/CD154 interactions at the interface of tolerance and immunity [7]
- Research article The significance of OX40 and OX40L to T-cell biology and immune disease [8]
- Research article The role of CD40 and CD154/CD40L in dendritic cells [9]
- Research article The CD40/CD40 ligand system: linking inflammation with atherothrombosis [10]
References
- Cognasse F, Duchez AC, Audoux E, Ebermeyer T, Arthaud CA, Prier A, et al.. Platelets as Key Factors in Inflammation: Focus on CD40L/CD40. . 2022. PMID 35185916 · DOI · PMC8850464
- Rossetti RAM, Lorenzi NPC, Yokochi K, Rosa MBSF, Benevides L, Margarido PFR, et al.. B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses. . 2018. PMID 29975708 · DOI · PMC6033398
- Saliba DG, Céspedes-Donoso PF, Bálint Š, Compeer EB, Korobchevskaya K, Valvo S, et al.. Composition and structure of synaptic ectosomes exporting antigen receptor linked to functional CD40 ligand from helper T cells. . 2019. PMID 31469364 · DOI · PMC6748831
- Subauste CS. Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy. . 2026. PMID 42123447 · DOI · PMC13163484
- Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009. PMID 19426221 · DOI · PMC3826168
- Schönbeck U, Libby P. The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci. 2001. PMID 11229815 · DOI · PMC11146501
- Quezada SA, Jarvinen LZ, Lind EF, Noelle RJ. CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol. 2004. PMID 15032580 · DOI
- Croft M, So T, Duan W, Soroosh P. The significance of OX40 and OX40L to T-cell biology and immune disease. Immunol Rev. 2009. PMID 19426222 · DOI · PMC2729757
- Ma DY, Clark EA. The role of CD40 and CD154/CD40L in dendritic cells. Semin Immunol. 2009. PMID 19524453 · DOI · PMC2749083
- Antoniades C, Bakogiannis C, Tousoulis D, Antonopoulos AS, Antonopoulos AS, Stefanadis C. The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J Am Coll Cardiol. 2009. PMID 19679244 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.