title: Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency.
abstract: 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 Km, 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: F X
authors.initials: FX
authors.lastname: Arredondo-Vega
authors.forename: J
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: S
authors.initials: S
authors.lastname: Chaffee
authors.forename: I
authors.initials: I
authors.lastname: Santisteban
authors.forename: E
authors.initials: E
authors.lastname: Reisner
authors.forename: M S
authors.initials: MS
authors.lastname: Povey
authors.forename: M S
authors.initials: MS
authors.lastname: Hershfield
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015703:Antigens, CD / Q000032:analysis; D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology*; D007376:Interleukin-2 / Q000494:pharmacology; D009154:Mutation; D009700:Nucleoside Deaminases / Q000172:deficiency* / Q000378:metabolism*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase