期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.02084
关键词
T-cell replication; TREC; TRG; primary immunodeficiency; newborn screening; aging
类别
资金
- Jeffrey Modell Foundation
- NHMRC Senior Research Fellowship [GNT1117687]
Quantification of T-cell receptor excision circles (TRECs) has impacted on human T-cell research, but interpretations on T-cell replication have been limited due to the lack of a genomic coding joint. We here overcome this limitation with multiplex TRG rearrangement quantification (detecting similar to 0.98 alleles per TCR alpha beta+ T cell) and the HSB-2 cell line with a retrovirally introduced TREC construct. We uncovered <5 cell divisions in naive and > 10 cell divisions in effector memory T-cell subsets. Furthermore, we show that TREC dilution with age in healthy adults results mainly from increased T cell replication history. This proliferation was significantly increased in patients with predominantly antibody deficiency. Finally, Guthrie cards of neonates with Down syndrome have fewer T and B cells than controls, with similar T-cell and slightly higher B-cell replication. Thus, combined analysis of TRG coding joints and TREC signal joints can be utilized to quantify in vivo T-cell replication, and has direct applications for research into aging, immunodeficiency, and newborn screening.
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