Quantification of T-cell and B-cell replication history in aging, immunodeficiency, and newborn screening

Ruud H.J. Verstegen, Pei M. Aui, Eliza Watson, Samuel De Jong, Sophinus J.W. Bartol, Julian J. Bosco, Paul U. Cameron, Robert G. Stirling, Esther de Vries, Jacques J.M. van Dongen, Menno C. van Zelm

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Abstract

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 <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.

Original languageEnglish
Article number2084
Number of pages13
JournalFrontiers in Immunology
Volume10
Issue numberAUG
DOIs
Publication statusPublished - Aug 2019

Keywords

  • Aging
  • Newborn screening
  • Primary immunodeficiency
  • T-cell replication
  • TREC
  • TRG

Cite this

Verstegen, R. H. J., Aui, P. M., Watson, E., De Jong, S., Bartol, S. J. W., Bosco, J. J., Cameron, P. U., Stirling, R. G., de Vries, E., van Dongen, J. J. M., & van Zelm, M. C. (2019). Quantification of T-cell and B-cell replication history in aging, immunodeficiency, and newborn screening. Frontiers in Immunology, 10(AUG), [2084]. https://doi.org/10.3389/fimmu.2019.02084