Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency.
J Clin Invest
; 86(2): 444-52, 1990 Aug.
Article
em En
| MEDLINE
| ID: mdl-1974554
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. 26316291-16296). 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Adenosina Desaminase
/
Síndromes de Imunodeficiência
/
Nucleosídeo Desaminases
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
1990
Tipo de documento:
Article