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.

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Keywords Aging, Newborn screening, Primary immunodeficiency, T-cell replication, TREC, TRG
Persistent URL dx.doi.org/10.3389/fimmu.2019.02084, hdl.handle.net/1765/119607
Journal Frontiers in Immunology
Verstegen, R.H.J, Aui, P.M. (Pei M.), Watson, E. (Eliza), De Jong, S. (Samuel), Bartol, S.J.W, Bosco, J.J. (Julian J.), … 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). doi:10.3389/fimmu.2019.02084