Estimating Thymic Function Through Quantification of T-Cell Receptor Excision Circles

Analysis of immune reconstitution is of major importance in clinical settings such as following bone marrow transplantation or during anti-retroviral treatment of HIV-infected patients. In these patients, thymic function is essential for the reconstitution of a diversified T-cell receptor (TCR) repertoire. During thymopoiesis, several genetic rearrangements lead to the generation of fully functional TCR. By-products of these processes, the T-cell receptor excision circles (TRECs), are present in cells exported from the thymus but do not replicate during mitosis; they can thus be used as molecular markers for recent thymic emigrants. We demonstrate how thymic function can be assessed in a quantitative and noninvasive fashion in humans by estimating intrathymic precursor T-cell proliferation through the quantification of distinct TREC molecules in peripheral blood cells.