Masato Ogishi, Rockefeller University
Rui Yang, Rockefeller University
Rémy Rodriguez, University of Paris Cité
Dominic P Golec, National Institutes of Health
Emmanuel Martin, University of Paris Cité
Quentin Philippot, University of Paris Cité
Jonathan Bohlen, University of Paris Cité
Simon J Pelham, Rockefeller University
Andrés Augusto Arias, University of Antioquia UdeA
Taushif Khan, Research Branch
Manar Ata, Research Branch
Fatima Al Ali, Research Branch
Flore Rozenberg, University of Paris
Xiao-Fei Kong, Rockefeller University
Maya Chrabieh, University of Paris Cité
Candice Laine, University of Paris Cité
Wei-Te Lei, Rockefeller University
Ji Eun Han, Rockefeller University
Yoann Seeleuthner, University of Paris Cité
Zenia Kaul, National Institutes of Health
Emmanuelle Jouanguy, Rockefeller University
Vivien Béziat, University of Paris Cité
Leila Youssefian, Thomas Jefferson UniversityFollow
Hassan Vahidnezhad, Thomas Jefferson UniversityFollow
V Koneti Rao, National Institutes of Health
Bénédicte Neven, Necker Hospital for Sick Children Assistance Publique-Hôpitaux de Paris (AP-HP)
Claire Fieschi, AP-HP Université de Paris
Davood Mansouri, Shahid Beheshti University of Medical Sciences
Mohammad Shahrooei, KU Leuven
Sevgi Pekcan, Necmettin Erbakan University
Gulsum Alkan, Selcuk University Faculty of Medicine
Melike Emiroğlu, Selcuk University Faculty of Medicine
Hüseyin Tokgöz, Necmettin Erbakan University
Jouni Uitto, Thomas Jefferson UniversityFollow
Fabian Hauck, Ludwig-Maximilians-Universität München
Jacinta Bustamante, Necker Hospital for Sick Children Assistance Publique-Hôpitaux de Paris (AP-HP)
Laurent Abel, University of Paris Cité
Sevgi Keles, Necmettin Erbakan University
Nima Parvaneh, Tehran University of Medical Sciences
Nico Marr, Necker Hospital for Sick Children
Pamela L Schwartzberg, National Institute of Allergy and Infectious Diseases
Sylvain Latour, University of Paris Cité
Jean-Laurent Casanova, Howard Hughes Medical Institute
Stéphanie Boisson-Dupuis, University of Paris Cité

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This article is the author’s final published version in Journal of Experimental Medicine, Volume 220, Issue 1, January 2023, Article number e20220484.

The published version is available at Copyright © Ogishi et al.


Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients' total lymphocytes secrete small amounts of IFN-γ, and CD4+, CD8+, DN αβ T, Vδ2+ γδ T, and MAIT cells display impaired IFN-γ production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-γ-producing T cell subsets, thereby underlying TB.

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This work is licensed under a Creative Commons Attribution 4.0 License.

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