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

Lyssia Belarif 1, 2 Caroline Mary 1, 2 Lola Jacquemont 3 Hoa Mai 3 Richard Danger 3 Jeremy Hervouet 1 David Minault 4 Virginie Thepenier 1, 2 Véronique Nerrière-Daguin 1 Elisabeth Nguyen 3 Sabrina Pengam 1, 2 Eric Largy 5, 6 Arnaud Delobel 5 Bernard Martinet 4 Stephanie Le Bas-Bernardet 7, 4 Sophie Brouard 7, 3 Jean-Paul Soulillou 3 Nicolas Degauque 7, 3 Gilles Blancho 7, 4 Bernard Vanhove 1, 2 Nicolas Poirier 1, 2
1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 OSE Immunotherapeutics [Nantes]
3 Team 4 - U1064 Inserm - CRTI - Immunoregulation And Immunointervention in Transplantation and Autoimmunity
U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
4 Team 3 - U1064 Inserm - CRTI - Immunotherapy in Transplantation And Autoimmunity
U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
5 Quality Assistance S.A [Thuin, Belgium]
6 ARNA - Acides Nucléiques : Régulations Naturelle et Artificielle
7 ITUN - Institut de transplantation urologie-néphrologie
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 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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Lyssia Belarif, Caroline Mary, Lola Jacquemont, Hoa Mai, Richard Danger, et al.. IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation in primates. Nature Communications, Nature Publishing Group, 2018, 9 (1), ⟨10.1038/s41467-018-06804-y⟩. ⟨inserm-02023397⟩

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