ArticlePloS one2012
In vivo depletion of lymphotoxin-alpha expressing lymphocytes inhibits xenogeneic graft-versus-host-disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Tensor-based integration of time-series measurements reveals relationships between underlying disease, early injury, and T cell polarization in liver transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Correlations between tear lymphocytotoxin-a (LT-α) level and disease severity in adult keratoconus.Frontiers in medicine · 2025Article
- Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants.Frontiers in immunology · 2024Article
- Role of lymphotoxin alpha as a new molecular biomarker in revolutionizing tear diagnostic testing for dry eye disease.International journal of ophthalmology · 2023Review
- Novel Humanized Peripheral Blood Mononuclear Cell Mouse Model with Delayed Onset of Graft-versus-Host Disease for Preclinical HIV Research.Journal of virology · 2022Article
- Ophthalmic manifestations are associated with reduced tear lymphotoxin-α levels in chronic ocular graft-versus-host disease.BMC ophthalmology · 2022Article
- Regulatory T Cells Condition Lymphatic Endothelia for Enhanced Transendothelial Migration.Cell reports · 2020Article
- Tertiary Lymphoid Structures: Autoimmunity Goes Local.Frontiers in immunology · 2018Review
- Lymphotoxin signalling in tertiary lymphoid structures and immunotherapy.Cellular & molecular immunology · 2017Review
- Evaluating the Use of Antibody Variable Region (Fv) Charge as a Risk Assessment Tool for Predicting Typical Cynomolgus Monkey Pharmacokinetics.The Journal of biological chemistry · 2015Article
- Restoration of peripheral blood natural killer and B cell levels in patients affected by rheumatoid and psoriatic arthritis during etanercept treatment.Clinical and experimental immunology · 2014Article
- Dimerization of LTβR by LTα1β2 is necessary and sufficient for signal transduction.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Clinical targeting of the TNF and TNFR superfamilies.Nature reviews. Drug discovery · 2013Review
- Controlling herpetic stromal keratitis by modulating lymphotoxin-alpha-mediated inflammatory pathways.Microbes and infectionArticle
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Graft-versus-host disease (GVHD) is a major barrier to successful allogeneic hematopoietic cell transplantation and is largely mediated by activated donor lymphocytes. Lymphotoxin (LT)-α is expressed by subsets of activated T and B cells, and studies in preclinical models demonstrated that targeted depletion of these cells with a mouse anti-LT-α monoclonal antibody (mAb) was efficacious in inhibiting inflammation and autoimmune disease. Here we demonstrate that LT-α is also upregulated on activated human donor lymphocytes in a xenogeneic model of GVHD and targeted depletion of these donor cells ameliorated GVHD. A depleting humanized anti-LT-α mAb, designated MLTA3698A, was generated that specifically binds to LT-α in both the soluble and membrane-bound forms, and elicits antibody-dependent cellular cytotoxicity (ADCC) activity in vitro. Using a human peripheral blood mononuclear cell transplanted SCID (Hu-SCID) mouse model of GVHD, the anti-human LT-α mAb specifically depleted activated LT-expressing human donor T and B cells, resulting in prolonged survival of the mice. A mutation in the Fc region, rendering the mAb incapable of mediating ADCC, abolished all in vitro and in vivo effects. These data support a role for using a depleting anti-LT-α antibody in treating immune diseases such as GVHD and autoimmune diseases.
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