Modification of cellular and humoral immunity by somatically reverted T cells in X-linked lymphoproliferative syndrome type 1

[...]this family was diagnosed with XLP1. [...]intracellular IL-10 expression and inducible costimulator expression were preferentially observed in SAP+ CD4+ T cells from P25.3 and M25.1 (Fig 2, E and F), suggesting that this contributed to the patient's partially impaired humoral immunity.2 These findings are consistent with the observation of adequate cellular and humoral immune reconstitution in a patient with XLP1 after HSCT, despite 5% donor chimerism.4 The present study confirmed that the prognosis for patients with XLP1 treated with HSCT is good; the treatment of patients who cannot undergo HSCT because of an unavailability of donors or extremely severe XLP1 currently remain a challenge. Deep sequencing of the PCR products was also performed using a HiSeq 2000 platform (depth >20,000).Generation of EBV-specific T-cell lines PBMCs were pulsed for 60 minutes with overlapping oligopeptides, covering the sequence of the LMP2A, BZLF1, and EBNA1 protein (PepTivator, Miltenyi Biotec), and then cultured with IL-4 (1,000 U/mL, R&D Systems) and IL-7 (1000 U/mL, R&D Systems, Minneapolis, Minn) for 10 days.E6 To measure cell proliferation, PBMCs were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE, 3 μM, eBioscience, San Diego, Calif) for 5 minutes at room temperature before pulse with overlapping oligopeptides or stimulus with T-cell activation and expansion (TAE) beads (anti-CD3/CD28/CD2 mAb beads, Miltenyi Biotec). Patient SH2D1A mutation SAP expression Clinical presentation EBV status HSCT (age at HSCT) Outcome (age at death or presence) 1.1 ND ND Hypo-γ, LPD + – Died (12, posttransfusion GvHD) 1.2 D33Y ND Hypo-γ, LPD + + (7) Alive (28) 2.1 R55X ND FIM + – Died (3, FIM) 3.1 R55X ND FIM + – Died (2, FIM) 3.2 R55X ND FIM + – Died (2, FIM) 4.1 c.117C>T ND FIM + – Died (2, FIM) 4.2 c.117C>T Deficient Lymphoma, vasculitis, HLH – – Died (14, HLH) 5.1 del of whole gene ND FIM + – Died (1, FIM) 6.1 G27S ND FIM + – Died (1, FIM) 7.1 ND ND Hypo-γ, aplastic anemia + – Died (1, sepsis) 7.2 H8D Deficient Hypo-γ, vasculitis – + (24) Alive (36) 8.1 c.285delA, fs ND FIM + – Died (1, FIM) 9.1 R55X Deficient Hypo-γ + + (8) Alive (24) 9.2 R55X Deficient FIM + + (6) Died (6, sepsis) 10.1 G49V Deficient Lymphoma + + (4) Alive (21) 10.2 G49V Deficient Healthy – + (1) Alive (10) 11.1 del of exons 3, 4 ND FIM + – Died (1, FIM) 11.2. del of exons 3, 4 Deficient FIM + – Died (2, FIM) 11.3 del of exons 3, 4 Deficient Healthy – + (0.7) Alive (15) 12.1 S34G Deficient