Dual T cell– and B cell–intrinsic deficiency in humans with biallelic RLTPR mutations
Open Access
- 19 September 2016
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 213 (11), 2413-2435
- https://doi.org/10.1084/jem.20160576
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.Keywords
Funding Information
- Institut National de la Santé et de la Recherche Médicale
- Paris Descartes University
- French National Research Agency (ANR-10-IAHU-01)
- National Agency for Research on AIDS and Viral Hepatitis (ANRS-13292)
- St. Giles Foundation
- ANRS (n°13318)
- National Institute of Allergy and Infectious Diseases (5T32AI007512)
- ANRS (ANR-13-PDOC-0025-01)
- National Health and Medical Research Council
- Australian-American Fulbright Commission
- National Institute of Allergy and Infectious Diseases (R01AI100887-01)
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