Age-dependent incidence, time course, and consequences of thymic renewal in adults

Frances T. Hakim, Sarfraz A. Memon, Rosemarie Cepeda, Elizabeth C. Jones, Catherine K. Chow, Claude Kasten-Sportes, Jeanne Odom, Barbara A. Vance, Barbara L. Christensen, Crystal L. Mackall, Ronald E. Gress

Research output: Contribution to journalArticle

265 Scopus citations

Abstract

Homeostatic regulation of T cells involves an ongoing balance of new T cell generation, peripheral expansion, and turnover. The recovery of T cells when this balance is disrupted provides insight into the mechanisms that govern homeostasis. In a long-term, single cohort study, we assessed the role of thymic function after autologous transplant in adults, correlating serial computed tomography imaging of thymic size with concurrent measurements of peripheral CD4+ T cell populations. We established the age-dependent incidence, time course, and duration of thymic enlargement in adults and demonstrated that these changes were correlated with peripheral recovery of naive CD45RA +CD62L+ and signal-joint TCR rearrangement excision circle-bearing CD4+ populations with broad TCR diversity. Furthermore, we demonstrated that renewed thymopoiesis was critical for the restoration of peripheral CD4+ T cell populations. This recovery encompassed the recovery of normal CD4+ T cell numbers, a low ratio of effector to central memory cells, and a broad repertoire of TCR Vβ diversity among these memory cells. These data define the timeline and consequences of renewal of adult thymopoietic activity at levels able to quantitatively restore peripheral T cell populations. They further suggest that structural thymic regrowth serves as a basis for the regeneration of peripheral T cell populations.

Original languageEnglish (US)
Pages (from-to)930-939
Number of pages10
JournalJournal of Clinical Investigation
Volume115
Issue number4
DOIs
StatePublished - Apr 2005

ASJC Scopus subject areas

  • Medicine(all)

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    Hakim, F. T., Memon, S. A., Cepeda, R., Jones, E. C., Chow, C. K., Kasten-Sportes, C., Odom, J., Vance, B. A., Christensen, B. L., Mackall, C. L., & Gress, R. E. (2005). Age-dependent incidence, time course, and consequences of thymic renewal in adults. Journal of Clinical Investigation, 115(4), 930-939. https://doi.org/10.1172/JCI200522492