ArticleClinical and experimental immunology2010
CD6 synergistic co-stimulation promoting proinflammatory response is modulated without interfering with the activated leucocyte cell adhesion molecule interaction.
Article in Clinical and experimental immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts.Frontiers in immunology · 2021Pooled it
- Phenotypic and functional characterization of the CD6-ALCAM T-cell co-stimulatory pathway after allogeneic cell transplantation.Haematologica · 2022Trial
- A two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19.Expert opinion on biological therapy · 2021Trial
- Use of a Humanized Anti-CD6 Monoclonal Antibody (Itolizumab) in Elderly Patients with Moderate COVID-19.Gerontology · 2020Trial
- Trial
- Trial
- Anti-CD6 monoclonal antibody UMCD6 induces CD6 internalization, remodels costimulatory receptor availability, and modulates CD4Frontiers in immunology · 2026Article
- Review
- Deciphering antigen-specific T cell navigation tactics and cancer immune evasion in co-cultures.Communications biology · 2025Article
- ALCAM on human oligodendrocytes mediates CD4 T cell adhesion.Brain : a journal of neurology · 2024Article
- ALCAM-mediated cDC1 CD8 T cells interactions are suppressed in advanced lung tumors.Oncoimmunology · 2024Article
- The TSP1-CD47-SIRPα interactome: an immune triangle for the checkpoint era.Cancer immunology, immunotherapy : CII · 2023Review
- Multi-omics analysis identifies IgG2b class-switching with ALCAM-CD6 co-stimulation in joint-draining lymph nodes during advanced inflammatory-erosive arthritis.Frontiers in immunology · 2023Article
- Human variation in population-wide gene expression data predicts gene perturbation phenotype.iScience · 2022Article
- An Exploratory Study of Itolizumab on the Preservation of Beta Cell Function in Adults with Recent-Onset Type 1 Diabetes.Journal of clinical medicine · 2022Article
- The CD6/ALCAM pathway promotes lupus nephritis via T cell-mediated responses.The Journal of clinical investigation · 2022Article
- Clinical drug therapies and biologicals currently used or in clinical trial to treat COVID-19.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Recent advances in antibody-based immunotherapy strategies for COVID-19.Journal of cellular biochemistry · 2021Review
- Disease-drug and drug-drug interaction in COVID-19: Risk and assessment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CD6 membrane-proximal scavenger receptor cysteine-rich domain (SRCR3) includes the activated leucocyte cell adhesion molecule (ALCAM) binding site. CD6-ALCAM mediates a low-affinity interaction and their long-term engagement contributes to the immunological synapse. Their ligation may play a dual function, facilitating stable adhesion between the antigen-presenting cells and T cells during the early activation phase and later in the proliferative phase of the immune response. This study explored the strength of the CD6 co-stimulatory effect and whether CD6 co-stimulation with its natural ligand ALCAM also contributes to the lymphocyte effector differentiation. It was found that CD6-ALCAM interaction in vitro induced a synergistic co-stimulation of normal human peripheral blood mononuclear cells, defined by Bliss analysis. CD6 co-stimulation enhanced the CD3 proliferative efficacy by 23-34%. Moreover, a fivefold increment in the CD25 molecules number with a distinct gene transcription profile associated with cell activation, differentiation, survival and adhesion molecules was observed over CD3 single activation. Additionally, CD6 co-stimulation in excess interleukin (IL)-2 promotes a preferentially proinflammatory response. Besides, a CD6 membrane-distal domain (SRCR1)-specific non-depleting monoclonal antibody (mAb) inhibited the induced proliferation in the presence of ALCAM, reducing interferon-γ, IL-6 and tumour necrosis factor-α production. These results suggest that CD6 co-stimulation enhances the intrinsic activity of the CD3 activation pathway and contributes to the T helper type 1 subset commitment, enhancing the IL-2 sensitivity of recent activated human lymphocytes. It supports the role of CD6 as a susceptibility gene for pathological autoimmunity leading to tissue inflammation, and its relevance for targeted therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.