Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis

Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis

<p dir="ltr">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 s...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Masato Ogishi (699705) (author)
مؤلفون آخرون: Rui Yang (293531) (author), Rémy Rodriguez (19570255) (author), Dominic P. Golec (8787620) (author), Emmanuel Martin (95724) (author), Quentin Philippot (558140) (author), Jonathan Bohlen (5368448) (author), Simon J. Pelham (18519930) (author), Andrés Augusto Arias (15274984) (author), Taushif Khan (691254) (author), Manar Ata (9046473) (author), Fatima Al Ali (13210926) (author), Flore Rozenberg (243050) (author), Xiao-Fei Kong (385546) (author), Maya Chrabieh (18519933) (author), Candice Laine (19570258) (author), Wei-Te Lei (5106497) (author), Ji Eun Han (18519936) (author), Yoann Seeleuthner (10232517) (author), Zenia Kaul (19570261) (author), Emmanuelle Jouanguy (64694) (author), Vivien Béziat (204259) (author), Leila Youssefian (12476328) (author), Hassan Vahidnezhad (12476331) (author), V. Koneti Rao (6750395) (author), Bénédicte Neven (5900393) (author), Claire Fieschi (64700) (author), Davood Mansouri (353320) (author), Mohammad Shahrooei (847633) (author), Sevgi Pekcan (4266331) (author), Gulsum Alkan (18551617) (author), Melike Emiroğlu (19570264) (author), Hüseyin Tokgöz (12027974) (author), Jouni Uitto (307381) (author), Fabian Hauck (7010126) (author), Jacinta Bustamante (64702) (author), Laurent Abel (69833) (author), Sevgi Keles (13851562) (author), Nima Parvaneh (353296) (author), Nico Marr (349853) (author), Pamela L. Schwartzberg (19570267) (author), Sylvain Latour (266419) (author), Jean-Laurent Casanova (64712) (author), Stéphanie Boisson-Dupuis (64693) (author)
منشور في: 2022
الموضوعات:
Biological sciences
Genetics
Biomedical and clinical sciences
Immunology
Inborn Errors of Immunity
Tuberculosis (TB)
EBV (Epstein-Barr Virus)
Mitogens
Autologous B Lymphocytes
T Cell Subsets
Immune System Defects
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الملخص:<p dir="ltr">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<sup>+</sup> αβ T lymphocytopenia with a concomitant expansion of CD4<sup>−</sup>CD8<sup>−</sup> double-negative (DN) αβ and Vδ2− γδ T lymphocytes, both displaying a unique CD38<sup>+</sup>CD45RA<sup>+</sup>T<sup>-</sup>bet<sup>+</sup>EOMES<sup>−</sup> 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<sup>+</sup>, CD8<sup>+</sup>, 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Experimental Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1084/jem.20220484" target="_blank">https://dx.doi.org/10.1084/jem.20220484</a></p>

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