Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon ageing.

Molecular immunology

PubMedID: 23000520

van der Weerd K, Dik WA, Schrijver B, Bogers AJ, Maat AP, van Nederveen FH, van Hagen PM, Van Dongen JJ, Langerak AW, Staal FJ. Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon ageing. Mol Immunol. 2013;53(3):302-12.
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 V?-J? TREC assay, which we used together with an adjusted dREC-?Ja 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.