Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon ageing |
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Authors: | Kim van der Weerd Willem A Dik Benjamin Schrijver Ad JJC Bogers Alexander PWM Maat Francien H van Nederveen P Martin van Hagen Jacques JM van Dongen Anton W Langerak Frank JT Staal |
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Institution: | 1. Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;2. Department of Cardiothoracic Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;3. Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;4. Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;5. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands |
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Abstract: | T-cell receptor (TCR) repertoire diversity, thymic output, clonal size and peripheral T-lymphocyte numbers largely depend on intra-thymic and post-thymic T-lymphocyte proliferation. However, quantitative insight into thymocyte and T-lymphocyte proliferation is still lacking. We developed a new TCRG-based TCR excision circle (TREC) assay, the Vγ-Jγ TREC assay, which we used together with an adjusted δREC-ψJα TREC assay to quantify the proliferative history of human thymocyte and T-lymphocyte subpopulations from children and adults. This revealed that thymocytes undergo ~6–8 intra-thymic cell divisions from the double negative (DN) 3 developmental stage onwards, which appeared independent of age. Thus thymocyte proliferation after the DN3 developmental stages is stable and therefore not contributing to the reduced thymic output upon ageing. Cord blood naive T lymphocytes had already undergone ~2–3 post-thymic cell divisions, which increased to ~6–7 cell divisions in naive T lymphocytes of middle-aged adults, indicating the importance of homeostatic naive T-lymphocyte proliferation from a young age onwards in the maintenance of peripheral T-lymphocyte numbers. In conclusion, our data provide quantitative insight into the proliferative history of thymocyte and T-lymphocyte subpopulations and alterations herein upon ageing. This novel TREC assay approach could prove valuable in immune status monitoring in a variety of conditions. |
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