Quantification of T-Cell and B-Cell Replication History in Aging, Immunodeficiency, and Newborn Screening
Ruud HJ Verstegen, Pei M Aui, Eliza Watson, Samuel De Jong, Sophinus JW Bartol, Julian J Bosco, Paul U Cameron, Robert G Stirling, Esther de Vries, Jacques JM van Dongen, Menno C van Zelm
FRONTIERS IN IMMUNOLOGY | FRONTIERS MEDIA SA | Published : 2019
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 ~0.98 alleles per TCRαβ+ T cell) and the HSB-2 cell line with a retrovirally introduced TREC construct. We uncovered 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, Guth..View full abstract
Awarded by NHMRC Senior Research Fellowship
This work was supported by The Jeffrey Modell Foundation, and an NHMRC Senior Research Fellowship to MvZ (GNT1117687).