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.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
van der Weerd K,Dik WA,Schrijver B,Bogers AJ,Maat AP,van Nederveen FH,van Hagen PM,van Dongen JJ,Langerak AW,Staal FJdoi
10.1016/j.molimm.2012.08.019subject
Has Abstractpub_date
2013-03-01 00:00:00pages
302-12issue
3eissn
0161-5890issn
1872-9142pii
S0161-5890(12)00378-1journal_volume
53pub_type
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