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, Aziz Belkadi, Gaspard Kerner, Lazaro Lorenzo, Caroline Deswarte, Maya Chrabieh, Etienne Patin, Quentin B. Vincent, Ingrid Müller-Fleckenstein, Bernhard Fleckenstein, Fatima Ailal, Lluis Quintana-MurciSylvie Fraitag, Marie Alexandra Alyanakian, Marianne Leruez-Ville, Capucine Picard, Anne Puel, Jacinta Bustamante, Stéphanie Boisson-Dupuis, Marie Malissen, Bernard Malissen, Laurent Abel, Alain Hovnanian, Luigi D. Notarangelo, Emmanuelle Jouanguy, Stuart G. Tangye, Vivien Béziat, Jean Laurent Casanova

Research output: Contribution to journalArticle

39 Citations (Scopus)


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
Issue number11
Publication statusPublished - 1 Jan 2016


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Wang, Y., Ma, C. S., 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, Q. B., Müller-Fleckenstein, I., Fleckenstein, B., Ailal, F., ... 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