Figure 1
Normal γc surface expression and a lack of constitutive signaling through the IL receptor complex.
(A) Representation of T cell recovery following gene therapy in 10 patients with SCID-X1. The immunological reconstitution of patient 8 (P8) to normal levels is indicated in red up to 3 weeks prior to diagnosis of leukemia. (B) Expression of γc on the surface of leukemic blasts measured by flow cytometry was within the normal range of control peripheral blood T cells. (C) Phosphorylation of the tyrosine residue of STAT5 is indicative of signaling through the JAK-STAT pathway when relevant ILs bind to cell-surface receptor complexes containing γc. Insert shows the presence of phosphorylated STAT5 by flow cytometry in response to IL-7 and IL-15 from the patient and PBMCs from a control. The response to different cytokines and different concentrations of IL-7 is shown in the main panel. Constitutive phosphorylation of STAT5 is not detectable and is also not induced by IL-2 or IL-15. Unstim, unstimulated. (D) Spectratype analysis revealed a dominant TCR Vβ6b clone in both CD4+ and CD8+ cells (d717, at time of leukemia diagnosis), which disappeared following chemotherapy (d735), allowing the emergence of a normal distribution of clones (see also Supplemental Figure 1).
