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

Journal article

Publication Details

Author(s): 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, Mueller-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, Beziat V, Casanova JL
Journal: Journal of Experimental Medicine
Publication year: 2016
Volume: 213
Journal issue: 11
Pages range: 2413-2435
ISSN: 0022-1007


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-?B 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.

FAU Authors / FAU Editors

Fleckenstein, Bernhard Prof. Dr.
Lehrstuhl für Klinische und Molekulare Virologie

External institutions with authors

Boston Children's Hospital
Garvan Institute of Medical Research
Hospital Center University Rouen / Centre hospitalier universitaire de Rouen (CHU)
Immunology Center of Marseille-Luminy
Institut Pasteur
Istanbul University / İstanbul Üniversitesi
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
University Hassan II Casablanca / جامعة الحسن الثانی دارالبیضاء
University of Paris 5 - René Descartes / Université Paris V René Descartes

How to cite

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 RLTPR mutations. Journal of Experimental Medicine, 213(11), 2413-2435. https://dx.doi.org/10.1084/jem.20160576

Wang, Yi, et al. "Dual T cell- and B cell-intrinsic deficiency in humans with biallelic RLTPR mutations." Journal of Experimental Medicine 213.11 (2016): 2413-2435.


Last updated on 2018-09-10 at 02:28