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 Sportes, Jeanne Odom, Barbara A. Vance, Barbara L. Christensen, Crystal L. Mackall, Ronald E. Gress

Research output: Contribution to journalArticle

263 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 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Hakim, F. T., Memon, S. A., Cepeda, R., Jones, E. C., Chow, C. K., 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