Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria - Archive ouverte HAL
Journal Articles Cell Year : 2020

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

Rui Yang
Houda Elarabi
  • Function : Author
Jean-Marc Doisne
Peng Zhang
Jing Han
  • Function : Author
Masato Ogishi
Conor Gruber
Janet Markle
  • Function : Author
Fatima Al Ali
Mahbuba Rahman
  • Function : Author
Taushif Khan
Yoann Seeleuthner
Gaspard Kerner
Lucas Husquin
  • Function : Author
Julia Maclsaac
  • Function : Author
Mohamed Jeljeli
  • Function : Author
Abderrahmane Errami
  • Function : Author
Fatima Ailal
Michael Kobor
  • Function : Author
Carmen Oleaga-Quintas
  • Function : Author
Manon Roynard
Mathieu Bourgey
  • Function : Author
Jamila El Baghdadi
  • Function : Author
Stéphanie Boisson-Dupuis
Anne Puel
Fréderic Batteux
  • Function : Author
Flore Rozenberg
Nico Marr
Qiang Pan-Hammarström
Dusan Bogunovic
Lluis Quintana-Murci
Thomas Carroll
  • Function : Author
Cindy Ma
Laurent Abel
Aziz Bousfiha
James Di Santo
Laurie Glimcher
  • Function : Author
Philippe Gros
  • Function : Author
Stuart Tangye
Federica Sallusto
  • Function : Author
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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pasteur-03260339 , version 1 (02-01-2023)

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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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