IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation in primates

Lyssia Belarif, Caroline Mary, Lola Jacquemont, Hoa Le Mai, Richard Danger, Jeremy Hervouet, David Minault, Virginie Thepenier, Veronique Nerrière-Daguin, Elisabeth Nguyen, Sabrina Pengam, Eric Largy, Arnaud Delobel, Bernard Martinet, Stéphanie Bas-Bernardet, Sophie Brouard, Jean-Paul Soulillou, Nicolas Degauque, Gilles Blancho, Bernard Vanhove and Nicolas Poirier ()
Additional contact information
Lyssia Belarif: Université de Nantes
Caroline Mary: Université de Nantes
Lola Jacquemont: Université de Nantes
Hoa Le Mai: Université de Nantes
Richard Danger: Université de Nantes
Jeremy Hervouet: Université de Nantes
David Minault: Université de Nantes
Virginie Thepenier: Université de Nantes
Veronique Nerrière-Daguin: Université de Nantes
Elisabeth Nguyen: Université de Nantes
Sabrina Pengam: Université de Nantes
Eric Largy: Quality Assistance
Arnaud Delobel: Quality Assistance
Bernard Martinet: Université de Nantes
Stéphanie Bas-Bernardet: Université de Nantes
Sophie Brouard: Université de Nantes
Jean-Paul Soulillou: Université de Nantes
Nicolas Degauque: Université de Nantes
Gilles Blancho: Université de Nantes
Bernard Vanhove: Université de Nantes
Nicolas Poirier: Université de Nantes

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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-7Rα monoclonal antibodies (mAb) in non-human primates and show that, depending on the target epitope, a single injection of antagonistic anti-IL-7Rα 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-γ upon antigen restimulation ex vivo. These findings indicate that chronic antigen-specific memory T cell responses can be controlled by anti-IL-7Rα mAbs, promoting and maintaining remission in T-cell mediated chronic inflammatory diseases.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06804-y

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DOI: 10.1038/s41467-018-06804-y

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