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ESTABLISHMENT AND CHARACTERIZATION OF ADENOSINE DEAMINASE (ADA)-DEFICIENT T CELL LINES

Abstract

Congenital deficiency of the purine metabolic enzyme ADA causes severe combined immunodeficiency (SCID). The profound T lymphopenia characteristic of this disease has limited direct investigation of the cell most affected by deficiency of ADA. We have been successful in establishing both IL-2-dependent, non-transformed and HTLV-1 transformed T cell lines from eight consecutive ADA-deficient SCID patients. The lines obtained by either method are mature T cells by surface phenotype. These lines all display hypersensitivity to deoxyadenosine, characteristic of ADA deficiency, which is not reversed by deoxycytidine. Clones obtained by limiting dilution of one line show multiple unique rearrangeents of the T cell receptor beta gene suggesting clonal diversity among the circulating T cells of this patient, despite lymphopenia and SCID. Lines from 5 patients, all under three years old, have less than 1% normal ADA activity. Pharmacologic inhibitor studies suggest that this remaining activity is attributable to a non-specific aminohydrolase. In contrast, cells from two children ages 11 and 13 years are partially deficient with up to 10% normal ADA activity. An eighth SCID patient, previously found to totally lack erythrocyte ADA has approximately 50% normal ADA in a line derived from thymocytes. Analysis of the molecular basis for ADA deficiency in these lines shows that the majority have a grossly intact ADA gene, contain normal size ADA mRNA (1.6kb) and produce an ADA protein that is catalytically defective.

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Kohn, D., Selegue, J., Ballow, M. et al. ESTABLISHMENT AND CHARACTERIZATION OF ADENOSINE DEAMINASE (ADA)-DEFICIENT T CELL LINES. Pediatr Res 21, 313 (1987). https://doi.org/10.1203/00006450-198704010-00876

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