T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool

TLDR

T cell receptor gene rearrangements during thymic differentiation generate deletion circles, and their detection in peripheral T cells has been interpreted as evidence of extrathymic T cell production. The study aimed to trace the fate of V(D)J deletion circles in chickens, whose T cells are exclusively thymic. Using the avian model, the authors quantified Vγ-Jγ and Vβ-Dβ deletion circles in blood, spleen, intestines, and thymus, and monitored their decline after thymectomy. Deletion circles were present in all examined tissues, but thymectomy caused a gradual loss with a half‑life of about two weeks, indicating that while they do not mark in‑situ rearrangement, their levels reflect newly generated T cells entering the peripheral pool.

Abstract

Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells located in the peripheral lymphoid tissues has been viewed as evidence for the existence of extrathymic T cell generation. Because all of the T cells in chickens apparently are generated in the thymus, we have employed this avian model to determine the fate of the V(D)J deletion circles. In normal animals we identified TCR Vγ-Jγ and Vβ-Dβ deletion circles in the blood, spleen, and intestines, as well as in the thymus. Thymectomy resulted in the gradual loss of these DNA deletion circles in all of the peripheral lymphoid tissues. A quantitative PCR analysis of Vγ1-Jγ1 and Vβ1-Dβ deletion circles in splenic γδ and Vβ1 + αβ T cells indicated that their numbers progressively decline after thymectomy with a half-life of approximately 2 weeks. Although TCR deletion circles therefore cannot be regarded as reliable indicators of in situ V(D)J rearrangement, measuring their levels in peripheral T cell samples can provide a valuable index of newly generated T cells entering the T cell pool.