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

IL-7受体阻断可减弱灵长类动物的抗原特异性记忆T细胞反应和慢性炎症。

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作者: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 Le Bas-Bernardet ,Sophie Brouard ,Jean-Paul Soulillou ,Nicolas Degauque ,Gilles Blancho ,Bernard Vanhove ,Nicolas Poirier

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.

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