Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-06804-y
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Funding
- French Public Bank of Investment (Effimab) [I 1302011 W]
- Fondation pour la Recherche Medicale [LBS20130627235]
- Region of Pays de la Loire
- French government [ANR-10-IBHU-005]
- Nantes Metropole
- Pays de la Loire Region
- FP7 VISICORT project from the European Union's Seventh Framework Programme for research, technological development and demonstration [602470]
- National Research Agency via the investment of the future program [ANR-11-LABX-0016-01]
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Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Here we investigate the therapeutic efficacy and mechanism of new anti-human IL-7R alpha monoclonal antibodies (mAb) in non-human primates and show that, depending on the target epitope, a single injection of antagonistic anti-IL-7R alpha mAbs induces a long-term control of skin inflammation despite repeated antigen challenges in presensitized monkeys. No modification in T cell numbers, phenotype, function or metabolism is observed in the peripheral blood or in response to polyclonal stimulation ex vivo. However, long-term in vivo hyporesponsiveness is associated with a significant decrease in the frequency of antigen-specific T cells producing IFN-gamma upon antigen restimulation ex vivo. These findings indicate that chronic antigen-specific memory T cell responses can be controlled by anti-IL-7R alpha mAbs, promoting and maintaining remission in T cell mediated chronic inflammatory diseases.
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