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Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria

Rui Yang 1 Federico Mele 2 Lisa Worley 3 David Langlais 4 Jérémie Rosain 5, 6 Ibithal Benhsaien 7 Houda Elarabi Carys Croft 8, 9 Jean-Marc Doisne 8 Peng Zhang 1 Marc Weisshaar 10 David Jarrossay 2 Daniela Latorre 10 Yichao Shen 11 Jing Han Masato Ogishi Conor Gruber Janet Markle Fatima Al Ali Mahbuba Rahman Taushif Khan Yoann Seeleuthner Gaspard Kerner Lucas Husquin Julia Maclsaac Mohamed Jeljeli Abderrahmane Errami Fatima Ailal Michael Kobor Carmen Oleaga-Quintas Manon Roynard Mathieu Bourgey Jamila El Baghdadi Stéphanie Boisson-Dupuis Anne Puel Fréderic Batteux Flore Rozenberg Nico Marr Qiang Pan-Hammarström Dusan Bogunovic Lluis Quintana-Murci Thomas Carroll Cindy Ma Laurent Abel Aziz Bousfiha James Di Santo Laurie Glimcher Philippe Gros Stuart Tangye Federica Sallusto Jacinta Bustamante Jean-Laurent Casanova 
Abstract : Inborn errors of human interferon gamma (IFN-γ) immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and Vδ2+ γδ T lymphocytes, and of Mycobacterium-non reactive classic TH1 lymphocytes, with the residual populations of these cells also producing abnormally small amounts of IFN-γ. Other lymphocyte subsets develop normally but produce low levels of IFN-γ, with the exception of CD8+ αβ T and non-classic CD4+ αβ TH1∗ lymphocytes, which produce IFN-γ normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2+ γδ T cells) and IFN-γ production by them, with mycobacterium-specific, IFN-γ-producing, purely adaptive CD8+ αβ T, and CD4+ αβ TH1∗ cells unable to compensate for this deficit.
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Submitted on : Monday, June 14, 2021 - 6:51:12 PM
Last modification on : Thursday, October 20, 2022 - 3:10:07 PM

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Rui Yang, Federico Mele, Lisa Worley, David Langlais, Jérémie Rosain, et al.. Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria. Cell, 2020, 183 (7), pp.1826-1847.e31. ⟨10.1016/j.cell.2020.10.046⟩. ⟨pasteur-03260339⟩



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