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• W2116779251 abstract "Abstract We previously reported successful peripheral T cell-directed gene therapy in a boy with adenosine deaminase (ADA)−SCID. In the present study, to better understand the reconstitutive effect of this gene therapy on his immunological system, we investigated the in vivo kinetics and functional subsets of T cells in PBL. Apparent immunological improvements were obtained after infusion of transduced cells at more than 4 × 108 cells/kg/therapy/3 mo. Frequency of ADAcDNA-integrated cells in PBL, ADA activity in PBL and clinical improvement showed good correlation, even though CD8+ cells gradually became predominant in PBL. On the basis that polyethylene glycol (PEG)-ADA was maintained at the same dosage as before gene therapy, we consider that his immunological improvement resulted from the gene therapy itself. Most CD3+ cells in PBL after gene therapy expressed TCRαβ. Analysis of TCR repertoire based on TCR V region usage revealed no expansion of limited clones in his PBL. The T cell subset cells CD8+CDw60+ and CD8+CD27+CD45RA−, which are reported to provide substantial help to B cells, were maintained throughout the gene therapy. Furthermore, his reconstituted peripheral T cells helped normal B cells to produce substantial IgG in vitro. Expression of both Th1- and Th2-type cytokine genes was induced in his reconstituted T cells at the same comparably high level as in normal subjects. Collectively, these results provide evidence of persistent and distinct functions of transduced cells in this patient’s PBL after gene therapy." @default.
• W2116779251 created "2016-06-24" @default.
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• W2116779251 date "1999-08-15" @default.
• W2116779251 modified "2023-09-25" @default.
• W2116779251 title "In Vivo Kinetics of Transduced Cells in Peripheral T Cell-Directed Gene Therapy: Role of CD8+ Cells in Improved Immunological Function in an Adenosine Deaminase (ADA)−SCID Patient" @default.
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• W2116779251 doi "https://doi.org/10.4049/jimmunol.163.4.2256" @default.
• W2116779251 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10438969" @default.
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