Document Type
Article
Publication Date
1-2-2023
Abstract
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.
Recommended Citation
Ogishi, Masato; Yang, Rui; Rodriguez, Rémy; Golec, Dominic P; Martin, Emmanuel; Philippot, Quentin; Bohlen, Jonathan; Pelham, Simon J; Arias, Andrés Augusto; Khan, Taushif; Ata, Manar; Al Ali, Fatima; Rozenberg, Flore; Kong, Xiao-Fei; Chrabieh, Maya; Laine, Candice; Lei, Wei-Te; Han, Ji Eun; Seeleuthner, Yoann; Kaul, Zenia; Jouanguy, Emmanuelle; Béziat, Vivien; Youssefian, Leila; Vahidnezhad, Hassan; Rao, V Koneti; Neven, Bénédicte; Fieschi, Claire; Mansouri, Davood; Shahrooei, Mohammad; Pekcan, Sevgi; Alkan, Gulsum; Emiroğlu, Melike; Tokgöz, Hüseyin; Uitto, Jouni; Hauck, Fabian; Bustamante, Jacinta; Abel, Laurent; Keles, Sevgi; Parvaneh, Nima; Marr, Nico; Schwartzberg, Pamela L; Latour, Sylvain; Casanova, Jean-Laurent; and Boisson-Dupuis, Stéphanie, "Inherited Human ITK Deficiency Impairs IFN-γ Immunity and Underlies Tuberculosis" (2023). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 173.
https://jdc.jefferson.edu/dcbfp/173
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
36326697
Language
English
Comments
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 https://doi.org/10.1084/jem.20220484. Copyright © Ogishi et al.