Dual T cell– and B cell–intrinsic deficiency in humans with biallelic RLTPR mutations
| Autor: | Stuart G. Tangye, Marie Malissen, Caroline Deswarte, Lluis Quintana-Murci, Lazaro Lorenzo, Marianne Leruez-Ville, Capucine Picard, Jean-Laurent Casanova, Yi Wang, Anne Puel, Yun Ling, Vivien Béziat, Aziz Bousfiha, Aziz Belkadi, Fatima Ailal, Gaspard Kerner, Romain Roncagalli, Kathryn Payne, Marie-Alexandra Alyanakian, Quentin B. Vincent, Elena Crestani, Serge Jacquot, Etienne Patin, Laurent Abel, Luigi D. Notarangelo, Maya Chrabieh, Bernard Malissen, Stéphanie Boisson-Dupuis, Sylvie Fraitag, Jacinta Bustamante, Bernhard Fleckenstein, Ingrid Müller-Fleckenstein, Cindy S. Ma, Alain Hovnanian, Yildiz Camcioglu, Emmanuelle Jouanguy |
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| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male 0301 basic medicine T-Lymphocytes Interleukin 21 0302 clinical medicine Leukocytes Immunology and Allergy Cytotoxic T cell IL-2 receptor Child Research Articles B-Lymphocytes ZAP70 Microfilament Proteins NF-kappa B Cell Differentiation Natural killer T cell Pedigree 3. Good health Phenotype medicine.anatomical_structure Child Preschool Female Dimerization Signal Transduction Adult Adolescent Cell Survival T cell Immunology Naive B cell Receptors Antigen B-Cell Biology Article Immunophenotyping Young Adult 03 medical and health sciences Th2 Cells CD28 Antigens medicine Humans Alleles B cell Cell Proliferation Base Sequence HEK293 Cells 030104 developmental biology Mutation Th17 Cells Immunologic Memory 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20160576 |
| Popis: | In two complementary papers, Casanova, Malissen, and collaborators report the discovery of human RLTPR deficiency, the first primary immunodeficiency of the human CD28 pathway in T cells. Together, the two studies highlight the important and largely (but not completely) overlapping roles of RLTPR in T and B cells of humans and mice. Combined immunodeficiency (CID) refers to inborn errors of human T cells that also affect B cells because of the T cell deficit or an additional B cell–intrinsic deficit. In this study, we report six patients from three unrelated families with biallelic loss-of-function mutations in RLTPR, the mouse orthologue of which is essential for CD28 signaling. The patients have cutaneous and pulmonary allergy, as well as a variety of bacterial and fungal infectious diseases, including invasive tuberculosis and mucocutaneous candidiasis. Proportions of circulating regulatory T cells and memory CD4+ T cells are reduced. Their CD4+ T cells do not respond to CD28 stimulation. Their CD4+ T cells exhibit a "Th2" cell bias ex vivo and when cultured in vitro, contrasting with the paucity of "Th1," "Th17," and T follicular helper cells. The patients also display few memory B cells and poor antibody responses. This B cell phenotype does not result solely from the T cell deficiency, as the patients’ B cells fail to activate NF-κB upon B cell receptor (BCR) stimulation. Human RLTPR deficiency is a CID affecting at least the CD28-responsive pathway in T cells and the BCR-responsive pathway in B cells. |
| Databáze: | OpenAIRE |
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