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. Author manuscript; available in PMC: 2011 May 11.
Published in final edited form as: N Engl J Med. 2010 Nov 11;363(20):1918–1927. doi: 10.1056/NEJMoa1003548

Figure 2. Correction of Leukocyte Function after Gene Therapy (GT).

Figure 2

Formation of the immunologic synapse between natural killer (NK) cells and tumor cells (K562), which is impaired in patients with the Wiskott–Aldrich syndrome (WAS), is restored after GT. The localization of perforin is restored 1 year after GT in Patient 2, with an immunologic synapse similar in appearance to that in a sample from a healthy control subject (HC) and in contrast to that from a patient with WAS who did not undergo GT (Panel A). Differential interference contrast (DIC) microscopy shows normal formation of cellular conjugates. However, an overlay view of the immunofluorescence analysis shows that the perforin staining is localized close to the adjacent cells in a healthy control and in Patient 2 after therapy, in contrast to the findings in a patient with untreated WAS. NK-cell lytic activity is at least partially restored after GT in Patients 1 and 2, as compared with an untreated patient with WAS and a control subject (Panel B). Podosome formation is restored in a fraction of monocytes from both patients after GT, as confirmed at multiple time points, in comparison with values in a control sample (Panel C). T-cell proliferative responses are normalized 2 years after GT, after stimulation with phytohemagglutinin (PHA) or CD3, as compared with unstimulated (US) samples (Panel D). The skewed Vβ family repertoire for T-cell receptors (TCRs), which was observed in both Patients 1 and 2, has normalized after GT (Panel E). (For a complete set of TCR Vβ spectratyping, see Fig. 9 in the Supplementary Appendix.) The severe and therapy-refractory eczema in Patient 2 shows complete regression 2 years after GT (Panel F). The I bars indicate standard errors.