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


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.

Type Journal
Authors 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, D.; Chrabieh, M.; Patin, E.; Vincent, QB.; Muller-Fleckenstein, I.; Fleckenstein, B.; Ailal, F.; Quintana-Murci, L.; Fraitag, S.; Alyanakian, MA.; Leruez-Ville, M.; Capucine, P.; Puel, A.; Bustamante, J.; Boisson-Dupuis, S.; Malissen, M.; Malissen, B.; Abel, L.; Hovnanian, A.; Notarangelo, LD.; Jouanguy, E.; Tangye,
Published Date 2016-09-19
Published Volume 213
Published Issue 11
Published Pages 2413-2435
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version