T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation.
T cell differentiation in the thymus is characterized by a hierarchical order of rearrangement steps in the T cell receptor (TCR) genes, resulting in the joining of V, D, and J gene segments. During each of the rearrangement steps, DNA fragments between rearranging V, D, and J gene segments are deleted as circular excision products, the so-called TRECs (T cell receptor excision circles). TRECs are assumed to have a high over-time stability, but they can not multiply and consequently are diluted during T cell proliferation. It was recently suggested that quantitative detection of TRECs would allow for direct measurement of thymic output. The deltaRec-psiJalpha TREC appears to be the best marker, because the majority of thymocyte expansion occurs before this TREC is formed. However, apart from thymic output several other factors determine the TREC content of a T cell population, such as cell division and cell death. Likewise, the number of TRECs depends not only on thymic output, but also on the longevity of naive T cells. This warrants caution with regard to the interpretation of TREC data as measured in healthy and diseased individuals. deltaRec-psiJalpha TREC detection is a new and elegant tool for identification of recent thymic emigrants in the periphery, but further research is required for making quantitative estimations of thymic output with the use of TREC analysis.
Hazenberg
M D
MD
Department of Clinical Viro-Immunology, CLB, and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. M_Hazenberg@CLB.nl
Verschuren
M C
MC
Hamann
D
D
Miedema
F
F
van Dongen
J J
JJ
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers; D002454:Cell Differentiation; D002455:Cell Division; D015321:Gene Rearrangement; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors
D019380:Anti-HIV Agents; D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell