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

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Belarif, Lyssia | Mary, Caroline | Jacquemont, Lola | Mai, Hoa, Le | Danger, Richard | Hervouet, Jeremy | Minault, David | Thepenier, Virginie | Nerrière-Daguin, Véronique | Nguyen, Elisabeth | Pengam, Sabrina | Largy, Eric | Delobel, Arnaud | Martinet, Bernard | Le Bas-Bernardet, Stephanie | Brouard, Sophie | Soulillou, Jean-Paul | Degauque, Nicolas | Blancho, Gilles | Vanhove, Bernard | Poirier, Nicolas

Edité par CCSD ; Nature Publishing Group -

International audience. 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 resti-mulation 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.

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