title: Gene-transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase-deficient patient during gene therapy.
abstract: Adenosine deaminase (ADA) deficiency is the primary cause of severe combined immunodeficiency disease and has become a focus for developing innovative approaches to gene therapy. We previously described successful treatment of a Japanese ADA-deficient patient by periodic infusions of genetically modified autologous T lymphocytes transduced with a retroviral vector containing human ADA cDNA. In order to investigate whether polyclonality was restored by the gene therapy and whether the gene-transduced T lymphocytes persisted in the peripheral blood of the patient, we analyzed the T cell clonotype using a T cell receptor-specific RT-PCR/SSCP method. Oligoclonal T cell expansion was observed in every Vbeta family, and the expanded T cell clones were stable throughout the periodic gene therapy. Some of these T cell clones are likely carrying the vector, since they were identical to the clones selected by G418 resistance. Therefore, although it is uncertain when oligoclonal T cells started to expand and what percentage of the oligoclones carries the vector, the peripheral blood of the patient administered the gene therapy included oligoclonal T cells, some of which were identical to the ADA-gene-transduced clones.
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, Tokyo, 113-8655, Japan. misaki-tky@umin.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Misaki
authors.forename: I
authors.initials: I
authors.lastname: Ezaki
authors.forename: T
authors.initials: T
authors.lastname: Ariga
authors.forename: N
authors.initials: N
authors.lastname: Kawamura
authors.forename: Y
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000243:Adenosine Deaminase / Q000097:blood* / Q000172:deficiency* / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017690:Cell Transplantation; D018076:DNA, Complementary / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D018076:DNA, Complementary; D005839:Gentamicins; C010680:antibiotic G 418; D000243:Adenosine Deaminase