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


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Wang Y., Ma C. S. , Ling Y., Bousfiha A., Camcioglu Y. , Jacquot S., ...Daha Fazla

JOURNAL OF EXPERIMENTAL MEDICINE, cilt.213, ss.2413-2435, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 213 Konu: 11
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1084/jem.20160576
  • Dergi Adı: JOURNAL OF EXPERIMENTAL MEDICINE
  • Sayfa Sayıları: ss.2413-2435

Özet

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-kappa 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.