Lymphocyte Maturation in the Human Thymus

Schuurman, Henk Jan; Laarhoven, J. P. R. M. van; Broekhuizen, Roel; Spierenburg, Gerrit; Brekelmans, P; Figdor, C.G.; Bruyn, C. H. M. M. de; Kater, L.

doi:10.1111/j.1365-3083.1983.tb00889.x

Cited by 12 publications

(1 citation statement)

References 29 publications

(48 reference statements)

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“…In the case of ADA, a core region within a 1.3-kb segment of the first intron has been shown to play an important role in the high level of expression of this enzyme in the thymus and T lymphoblasts (20,21). dCyd kinase, like ADA and TdT, is expressed at the highest levels in thymocytes and leukemic T lymphoblasts and expression is downregulated during T-cell development (22). It will be of considerable interest to determine the factors contributing to the tissue-specific regulation of these three genes.…”

Section: Discussionmentioning

confidence: 99%

Genomic structure and chromosomal localization of the human deoxycytidine kinase gene.

Song

Walker

Chen

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Deoxycytidine kinase (NTP:deoxycytidine 5'-phosphotransferase, EC 2.7.1.74) is an enzyme that catalyzes phosphorylation of deoxyribonucleosides and a number of nucleoside analogs that are important in antiviral and cancer chemotherapy. Deficiency of this enzyme activity is associated with resistance to these agents, whereas increased enzyme activity is associated with increased activation of such compounds to cytotoxic nucleoside triphosphate derivatives. To characterize the regulation of expression of this gene, we have isolated genomic clones encompassing its entire coding and 5' flanking regions and delineated all the exon/intron boundaries. The gene extends over more than 34 kilobases on chromosome 4 and the coding region is composed of 7 exons ranging in size from 90 to 1544 base pairs (bp). The 5' flanking region is highly G+C-rich and contains four regions that are potential Spl binding sites. A 697-bp fragment encompassing 386 bp of 5' upstream region, the 250-bp frst exon, and 61 bp of the first intron was demonstrated to promote chloramphenicol acetyltransferase activity in a T-lymphoblast cell line and to have >6-fold greater activity in a Jurkat T-lymphoblast than in a Raji B-lymphoblast cell line. Our data suggest that these 5' sequences may contain elements that are important for the tissue-specific differences in deoxycytidine kinase expression.

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Section: Discussionmentioning

confidence: 99%

Genomic structure and chromosomal localization of the human deoxycytidine kinase gene.

Song

Walker

Chen

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Regulation of thymocyte proliferation and survival by deoxynucleosides. Deoxycytidine produced by thymic accessory cells protects thymocytes from deoxyguanosine toxicity and stimulates their spontaneous proliferation

Pénit

Papiernik

1986

Eur J Immunol

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Deoxyguanosine (dGuo) inhibits thymic blast DNA synthesis and then induces thymocyte cell death. The dGuo inhibitory action, measured with four different assays (spontaneous thymidine incorporation, immunofluorescent detection of 5-bromodeoxyuridine incorporation, dye exclusion, tetrazolium salt cleavage), was suppressed in the presence of supernatants from cultures containing phagocytic cells. In particular, we studied the anti-dGuo activity in supernatants from thymic reticulum cultures (TRS) and in those from phagocytic cells isolated from TR cultures (P-TR). The anti-dGuo substance was identified as deoxycytidine (dCyd) by high performance liquid chromatography and other physicochemical studies. Secretion of dCyd by P-TR is accompanied by thymidine but not by purine nucleoside secretion. A dual mechanism of thymocyte rescue by dCyd was demonstrated by a study of the dose-dependencies of dCyd-mediated prevention and reversal, respectively, of the dGuo inhibition. In addition to this exogenously added anti-dGuo action, dCyd and dCyd-containing TRS induced significant stimulation of spontaneous thymic blast proliferation, and the kinetics of both effects were identical. These findings might suggest that a major role of thymic phagocytic cells is the supply of pyrimidine nucleosides to thymocytes resulting in the maintenance of proliferation and protection of at least some thymic blasts from the toxic effects of dGTP accumulation. The role of this system in the intrathymic selection process is discussed.

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