Gene-transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase-deficient patient during gene therapy.

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.