{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:45:33Z","timestamp":1791294333503,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Understanding T cell homeostasis requires knowledge of the export rate of new T cells from the thymus, a rate that has been surprisingly difficult to estimate. TCR excision circle (TREC) content has been used as a proxy for thymic export, but this quantity is influenced by cell division and loss of naive T cells and is not a direct measure of thymic export. We present in this study a method for quantifying thymic export in humans by combining two simple mathematical models. One uses Ki67 data to calculate the rate of peripheral naive T cell production, whereas the other tracks the dynamics of TRECs. Combining these models allows the contributions of the thymus and cell division to the daily production rate of T cells to be disentangled. The method is illustrated with published data on Ki67 expression and TRECs within naive CD4+ T cells in healthy individuals. We obtain a quantitative estimate for thymic export as a function of age from birth to 20 years. The export rate of T cells from the thymus follows three distinct phases, as follows: an increase from birth to a peak at 1 year, followed by rapid involution until \u223c8 years, and then a more gradual decline until 20 years. The rate of involution shown by our model is compatible with independent estimates of thymic function predicted by thymic epithelial space. Our method allows nonintrusive estimation of thymic output on an individual basis and may provide a means of assessing the role of the thymus in diseases such as HIV.<\/jats:p>","DOI":"10.4049\/jimmunol.0900743","type":"journal-article","created":{"date-parts":[[2009,9,4]],"date-time":"2009-09-04T20:55:29Z","timestamp":1252097729000},"page":"4329-4336","source":"Crossref","is-referenced-by-count":125,"title":["Quantifying Thymic Export: Combining Models of Naive T Cell Proliferation and TCR Excision Circle Dynamics Gives an Explicit Measure of Thymic Output"],"prefix":"10.1093","volume":"183","author":[{"given":"Iren","family":"Bains","sequence":"first","affiliation":[{"name":"Immunobiology Unit, Institute of Child Health , London,","place":["United Kingdom"]},{"name":"Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolphe","family":"Thi\u00e9baut","sequence":"additional","affiliation":[{"name":"INSERM U897 Epidemiology and Biostatistics, Institut de Sant\u00e9 Publique, d\u2019Epidemiologie et de D\u00e9veloppement, Universit\u00e9 Victor Segalen Bordeaux 2 , Bordeaux,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Biology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Callard","sequence":"additional","affiliation":[{"name":"Immunobiology Unit, Institute of Child Health , London,","place":["United Kingdom"]},{"name":"Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,10,1]]},"reference":[{"key":"2026012811225537400_R1","first-page":"563","article-title":"The involution of the ageing human thymic epithelium is independent of puberty: a morphometric study.","volume-title":"Scand. J. Immunol.","year":"1985"},{"key":"2026012811225537400_R2","first-page":"2316","article-title":"Measurement and modeling of human T cell kinetics.","volume-title":"Eur. J. Immunol.","year":"2003"},{"key":"2026012811225537400_R3","first-page":"1036","article-title":"Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection.","volume-title":"Nat. Med.","year":"2000"},{"key":"2026012811225537400_R4","first-page":"6663","article-title":"Evidence for increased T cell turnover and decreased thymic output in HIV infection.","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012811225537400_R5","first-page":"351","article-title":"Decline in excision circles requires homeostatic renewal or homeostatic death of naive T cells.","volume-title":"J. Theor. Biol.","year":"2003"},{"key":"2026012811225537400_R6","first-page":"5480","article-title":"Quantifying the development of the peripheral naive CD4+ T cell pool in humans.","volume-title":"Blood","year":"2009"},{"key":"2026012811225537400_R7","first-page":"210","article-title":"Thymus cell migration: quantitative aspects of cellular traffic from the thymus to the periphery in mice.","volume-title":"Eur. J. Immunol.","year":"1980"},{"key":"2026012811225537400_R8","first-page":"559","article-title":"Autoradiographic analysis of lymphopoiesis and lymphocyte migration in mice bearing multiple thymus grafts.","volume-title":"J. Exp. Med.","year":"1966"},{"key":"2026012811225537400_R9","first-page":"3","article-title":"The generation and fate of thymocytes.","volume-title":"Semin. Immunol.","year":"1990"},{"key":"2026012811225537400_R10","first-page":"30","article-title":"Phenotypic and immunohistological analyses of the human adult thymus: evidence for an active thymus during adult life.","volume-title":"Cell. Immunol.","year":"1997"},{"key":"2026012811225537400_R11","first-page":"255","article-title":"Rapid turnover of effector-memory CD4+ T cells in healthy humans.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012811225537400_R12","first-page":"6115","article-title":"Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2008"},{"key":"2026012811225537400_R13","first-page":"690","article-title":"Changes in thymic function with age and during the treatment of HIV infection.","volume-title":"Nature","year":"1998"},{"key":"2026012811225537400_R14","first-page":"97","article-title":"Thymic function can be accurately monitored by the level of recent T cell emigrants in the circulation.","volume-title":"Immunity","year":"1998"},{"key":"2026012811225537400_R15","first-page":"609","article-title":"T-cell receptor \u03b1 locus V(D)J recombination by-products are abundant in thymocytes and mature T cells.","volume-title":"Mol. Cell. Biol.","year":"1996"},{"key":"2026012811225537400_R16","first-page":"789","article-title":"Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood.","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2026012811225537400_R17","first-page":"275","article-title":"Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function.","volume-title":"J. Exp. Med.","year":"2009"},{"key":"2026012811225537400_R18","first-page":"2808","article-title":"Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis.","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012811225537400_R19","first-page":"1499","article-title":"Homeostasis of the naive CD4+ T cell compartment during aging.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012811225537400_R20","first-page":"3270","article-title":"Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children.","volume-title":"Eur. J. Immunol.","year":"2007"},{"key":"2026012811225537400_R21","first-page":"2999","article-title":"IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner.","volume-title":"Blood","year":"2008"},{"key":"2026012811225537400_R22","first-page":"1987","article-title":"Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults.","volume-title":"Eur. J. Immunol.","year":"2005"},{"key":"2026012811225537400_R23","first-page":"769","article-title":"Life after the thymus: CD31+ and CD31\u2212 human naive CD4+ T-cell subsets.","volume-title":"Blood","year":"2009"},{"key":"2026012811225537400_R24","first-page":"1710","article-title":"Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.","volume-title":"J. Immunol.","year":"1984"},{"key":"2026012811225537400_R25","first-page":"31","article-title":"Cell cycle dependent expression and stability of the nuclear protein detected by Ki-67 antibody in HL-60 cells.","volume-title":"Cell Prolif.","year":"1992"},{"key":"2026012811225537400_R26","first-page":"1263","article-title":"Do cells cycle?.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1973"},{"key":"2026012811225537400_R27","first-page":"704","article-title":"Transition probability and the origin of variation in the cell cycle.","volume-title":"Nature","year":"1977"},{"key":"2026012811225537400_R28","first-page":"1815","article-title":"Regulation of cell reproduction.","volume-title":"Cancer Res.","year":"1968"},{"key":"2026012811225537400_R29","first-page":"3513","article-title":"Establishment of the CD4+ T-cell pool in healthy children and untreated children infected with HIV-1.","volume-title":"Blood","year":"2004"},{"key":"2026012811225537400_R30","first-page":"569","article-title":"Generation of functional thymocytes in the human adult.","volume-title":"Immunity","year":"1999"},{"key":"2026012811225537400_R31","first-page":"4215","article-title":"Identification of a human recent thymic emigrant phenotype.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2026012811225537400_R32","first-page":"725","article-title":"Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy.","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026012811225537400_R33","first-page":"43","article-title":"Cell death and maintenance of immunological memory.","volume-title":"Disc. Cont. Dyn. Sys. B","year":"2001"},{"key":"2026012811225537400_R34","first-page":"948","article-title":"Understanding the slow depletion of memory CD4+ T cells in HIV infection.","volume-title":"PLoS Med.","year":"2007"},{"key":"2026012811225537400_R35","first-page":"31","article-title":"Evidence for an essentially constant duration of DNA synthesis in renewing epithelia of the adult mouse.","volume-title":"J. Cell Biol.","year":"1963"},{"key":"2026012811225537400_R36","first-page":"239","article-title":"A cellular calculus for signal integration by T cells.","volume-title":"Nat. Immunol.","year":"2000"},{"key":"2026012811225537400_R37","first-page":"532","article-title":"Age-matched lymphocyte subpopulation reference values in childhood and adolescence: application of exponential regression analysis.","volume-title":"Eur. J. Haematol.","year":"2008"},{"key":"2026012811225537400_R38","first-page":"227","article-title":"Estimation and prediction of blood volume in infants and children.","volume-title":"Eur. J. Pediatr.","year":"1977"},{"key":"2026012811225537400_R39","first-page":"1","article-title":"CDC growth charts: United States.","volume-title":"Adv. Data","year":"2000"},{"key":"2026012811225537400_R40","first-page":"511","article-title":"Number and distribution of lymphocytes in man: a critical analysis.","volume-title":"Klin. Wochenschr.","year":"1974"},{"key":"2026012811225537400_R41","first-page":"5393","article-title":"Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2026012811225537400_R42","first-page":"834","article-title":"Age-related changes in the cellular composition of the thymus in children.","volume-title":"J. Allergy Clin. Immunol.","year":"2005"},{"key":"2026012811225537400_R43","first-page":"2851","article-title":"Effects of exogenous interleukin-7 on human thymus function.","volume-title":"Blood","year":"2002"},{"key":"2026012811225537400_R44","first-page":"757","article-title":"HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation.","volume-title":"Immunity","year":"2004"},{"key":"2026012811225537400_R45","first-page":"577","article-title":"Paradoxical age-related cell cycle quickening of human CD4+ lymphocytes: a role for cyclin D1 and calpain.","volume-title":"Exp. Gerontol.","year":"2004"},{"key":"2026012811225537400_R46","first-page":"2119","article-title":"Entrapment of recent thymic emigrants in lymphoid tissues from HIV-infected patients: association with HIV cellular viral load.","volume-title":"AIDS","year":"2002"},{"key":"2026012811225537400_R47","first-page":"794","article-title":"Limited CD4+ T-cell renewal in early HIV-1 infection: effect of highly active antiretroviral therapy.","volume-title":"Nat. Med.","year":"1998"},{"key":"2026012811225537400_R48","first-page":"973","article-title":"Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study.","volume-title":"J. Allergy Clin. Immunol.","year":"2003"},{"key":"2026012811225537400_R49","first-page":"1112","article-title":"Thymic size on chest radiograph and rapid disease progression in human immunodeficiency virus 1-infected children.","volume-title":"Pediatr. Infect. Dis. J.","year":"2001"},{"key":"2026012811225537400_R50","first-page":"2301","article-title":"High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.","volume-title":"J. Clin. Invest.","year":"1998"},{"key":"2026012811225537400_R51","first-page":"462","article-title":"Naive T cells are maintained in the periphery during the first 3 months of acute HIV-1 infection: implications for analysis of thymus function.","volume-title":"J. Clin. Immunol.","year":"2005"},{"key":"2026012811225537400_R52","volume-title":"Mathematica version 7.0","year":"2008"},{"key":"2026012811225537400_R53","volume-title":"R: A Language and Environment for Statistical Computing","year":"2008"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/7\/4329\/62689108\/9681.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/7\/4329\/62689108\/9681.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:23:58Z","timestamp":1769617438000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/183\/7\/4329\/8053161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10,1]]},"references-count":53,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2009,10,1]]},"published-print":{"date-parts":[[2009,10,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0900743","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,10]]},"published":{"date-parts":[[2009,10,1]]}}}