PARADOXICAL EXPRESSION OF ADENOSINE-DEAMINASE IN T-CELLS CULTURED FROM A PATIENT WITH ADENOSINE-DEAMINASE DEFICIENCY AND COMBINED IMMUNODEFICIENCY

T lymphocytes cultured from a patient (T.D.) with adenosine deaminase (ADA) deficiency expressed ADA activity in the normal range, inconsistent with her severe immunodeficiency, metabolic abnormalities, and with the absence of ADA activity in her B lymphocytes and other nucleated hematopoietic cells. ADA from T.D. T cells had normal K(m), heat stability, and sensitivity to ADA inhibitors. Examination of HLA phenotype and polymorphic DNA loci indicated that T.D. was neither chimeric nor a genetic mosaic. Amplified and subcloned ADA cDNA from ADA+ T.D. T cells was shown by allele-specific oligonucleotide hybridization to possess the same mutations (Arg101 → Trp, Arg211 → His) previously found in the ADA- T.D. B cell line GM 2606 (Akeson, A.L., D.A. Wiginton, M.R. Dusing, J.C. States, and J.J. Hutton. 1988 J. Biol. Chem. 263:16291-16296). Our findings suggest that one of these mutant alleles can be expressed selectively in IL-2-dependent T cells as stable, active enzyme. Cultured T cells from other patients with the Arg211 → His mutation did not express significant ADA activity, while some B cell lines from a patient with an Arg101 → Gln mutation have been found to express normal ADA activity. We speculate that Arg101 may be at a site that determines degradation of ADA by a protease that is under negative control by IL-2 in T cells, and is variably expressed in B cells. IL-2 might increase ADA expression in T cells of patients who possess mutations of Arg101.