Dual T cell- and B cell-intrinsic deficiency in humans with biallelic RLT PR mutations

Yi Wang, Cindy S. Ma, Yun Ling, Aziz Bousfiha, Yildiz Camcioglu, Serge Jacquot, Kathryn Payne, Elena Crestani, Romain Roncagalli, Abdelaziz Belkadi, Gaspard Kerner, Lazaro Lorenzo, Caroline Deswarte, Maya Chrabieh, Etienne Patin, Quentin B. Vincent, Ingrid M�ller-Fleckenstein, Bernhard Fleckenstein, Fatima Ailal, Lluis Quintana-MurciSylvie Fraitag, Marie Alexandra Alyanakian, Marianne Leruez-Ville, Capucine Picard, Anne Puel, Jacinta Bustamante, St�phanie Boisson-Dupuis, Marie Malissen, Bernard Malissen, Laurent Abel, Alain Hovnanian, Luigi D. Notarangelo, Emmanuelle Jouanguy, Stuart G. Tangye, Vivien B�ziat, Jean Laurent Casanova

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2413-2435
Number of pages23
JournalJournal of Experimental Medicine
Volume213
Issue number11
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

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B-Lymphocytes
T-Lymphocytes
Mutation
Th2 Cells
Mycoses
Candidiasis
Regulatory T-Lymphocytes
Helper-Inducer T-Lymphocytes
Antibody Formation
Communicable Diseases
Hypersensitivity
Tuberculosis
Phenotype
Lung
Skin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Wang, Y., Ma, C. S., Ling, Y., Bousfiha, A., Camcioglu, Y., Jacquot, S., ... Casanova, J. L. (2016). Dual T cell- and B cell-intrinsic deficiency in humans with biallelic RLT PR mutations. Journal of Experimental Medicine, 213(11), 2413-2435. https://doi.org/10.1084/jem.20160576

Dual T cell- and B cell-intrinsic deficiency in humans with biallelic RLT PR mutations. / Wang, Yi; Ma, Cindy S.; Ling, Yun; Bousfiha, Aziz; Camcioglu, Yildiz; Jacquot, Serge; Payne, Kathryn; Crestani, Elena; Roncagalli, Romain; Belkadi, Abdelaziz; Kerner, Gaspard; Lorenzo, Lazaro; Deswarte, Caroline; Chrabieh, Maya; Patin, Etienne; Vincent, Quentin B.; M�ller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Ailal, Fatima; Quintana-Murci, Lluis; Fraitag, Sylvie; Alyanakian, Marie Alexandra; Leruez-Ville, Marianne; Picard, Capucine; Puel, Anne; Bustamante, Jacinta; Boisson-Dupuis, St�phanie; Malissen, Marie; Malissen, Bernard; Abel, Laurent; Hovnanian, Alain; Notarangelo, Luigi D.; Jouanguy, Emmanuelle; Tangye, Stuart G.; B�ziat, Vivien; Casanova, Jean Laurent.

In: Journal of Experimental Medicine, Vol. 213, No. 11, 01.01.2016, p. 2413-2435.

Research output: Contribution to journalArticle

Wang, Y, Ma, CS, Ling, Y, Bousfiha, A, Camcioglu, Y, Jacquot, S, Payne, K, Crestani, E, Roncagalli, R, Belkadi, A, Kerner, G, Lorenzo, L, Deswarte, C, Chrabieh, M, Patin, E, Vincent, QB, M�ller-Fleckenstein, I, Fleckenstein, B, Ailal, F, Quintana-Murci, L, Fraitag, S, Alyanakian, MA, Leruez-Ville, M, Picard, C, Puel, A, Bustamante, J, Boisson-Dupuis, S, Malissen, M, Malissen, B, Abel, L, Hovnanian, A, Notarangelo, LD, Jouanguy, E, Tangye, SG, B�ziat, V & Casanova, JL 2016, 'Dual T cell- and B cell-intrinsic deficiency in humans with biallelic RLT PR mutations', Journal of Experimental Medicine, vol. 213, no. 11, pp. 2413-2435. https://doi.org/10.1084/jem.20160576
Wang, Yi ; Ma, Cindy S. ; Ling, Yun ; Bousfiha, Aziz ; Camcioglu, Yildiz ; Jacquot, Serge ; Payne, Kathryn ; Crestani, Elena ; Roncagalli, Romain ; Belkadi, Abdelaziz ; Kerner, Gaspard ; Lorenzo, Lazaro ; Deswarte, Caroline ; Chrabieh, Maya ; Patin, Etienne ; Vincent, Quentin B. ; M�ller-Fleckenstein, Ingrid ; Fleckenstein, Bernhard ; Ailal, Fatima ; Quintana-Murci, Lluis ; Fraitag, Sylvie ; Alyanakian, Marie Alexandra ; Leruez-Ville, Marianne ; Picard, Capucine ; Puel, Anne ; Bustamante, Jacinta ; Boisson-Dupuis, St�phanie ; Malissen, Marie ; Malissen, Bernard ; Abel, Laurent ; Hovnanian, Alain ; Notarangelo, Luigi D. ; Jouanguy, Emmanuelle ; Tangye, Stuart G. ; B�ziat, Vivien ; Casanova, Jean Laurent. / Dual T cell- and B cell-intrinsic deficiency in humans with biallelic RLT PR mutations. In: Journal of Experimental Medicine. 2016 ; Vol. 213, No. 11. pp. 2413-2435.
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AU - Camcioglu, Yildiz

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AU - Payne, Kathryn

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AU - Lorenzo, Lazaro

AU - Deswarte, Caroline

AU - Chrabieh, Maya

AU - Patin, Etienne

AU - Vincent, Quentin B.

AU - M�ller-Fleckenstein, Ingrid

AU - Fleckenstein, Bernhard

AU - Ailal, Fatima

AU - Quintana-Murci, Lluis

AU - Fraitag, Sylvie

AU - Alyanakian, Marie Alexandra

AU - Leruez-Ville, Marianne

AU - Picard, Capucine

AU - Puel, Anne

AU - Bustamante, Jacinta

AU - Boisson-Dupuis, St�phanie

AU - Malissen, Marie

AU - Malissen, Bernard

AU - Abel, Laurent

AU - Hovnanian, Alain

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AU - Jouanguy, Emmanuelle

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