Reevaluation of T cell receptor excision circles as a measure of human recent thymic emigrants.
The human thymus exports newly generated T cells to the periphery. As no markers have been identified for these recent thymic emigrants (RTE), it is presently impossible to measure human thymic output. T cell receptor excision circles (TREC) have been recently used to assess thymic output during both health and disease. Using a mathematical model, we quantify age-dependent changes both in the number of RTE generated per day and in TREC concentration during an 80-year lifespan. Through analyses, we demonstrate that RTE and peripheral T cell division have the same potential to affect TREC concentration at any age in healthy people. T cell death also influences TREC concentration, but to a lesser extent. During aging, our results indicate that thymic involution primarily induces an age-dependent decline in TREC concentrations within both CD4(+) and CD8(+) T cell populations. We further apply this model for studying TREC concentration during HIV-1 infection. Our analyses reveal that a decrease in thymic output is the major contributor to the decline in TREC concentration within CD4(+) T cells, whereas both increased peripheral T cell division and decreased thymic output induce the decline in TREC concentration within CD8(+) T cells. Therefore, we suggest that T cell turnover should be examined together with TREC concentration as a measure of RTE. If peripheral T cell division remains relatively unchanged, then TREC concentration indeed reflects thymic output.
Ye
Ping
P
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.
Kirschner
Denise E
DE
D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D017637:Clonal Deletion; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
D011948:Receptors, Antigen, T-Cell