Age-dependent incidence, time course, and consequences of thymic renewal in adults
Frances T. Hakim, … , Crystal L. Mackall, Ronald E. Gress
Frances T. Hakim, … , Crystal L. Mackall, Ronald E. Gress
Published April 1, 2005
Citation Information: J Clin Invest. 2005;115(4):930-939. https://doi.org/10.1172/JCI22492.
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Article

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

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.

Authors

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

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Figure 9

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Effect of renewed thymopoiesis and age on TCR repertoire diversity. (A) ...
Effect of renewed thymopoiesis and age on TCR repertoire diversity. (A) Repertoire diversity in naive versus memory CD4+ T cells in 2 individuals, patient A (Pt. A) and Pt. B, with less than 15% naive CD4+ T cells after 2–4 years. Representative spectratypes of several Vβ families demonstrate that naive CD4+ populations have polyclonal spectratypes, whereas memory/activated CD45RA– CD4+ T cells have more limited diversity. (B–D) Spearman correlation demonstrates that recovery of diverse CDR3 repertoire in memory/activated (CD45RA–) CD4+ T cells is correlated with recovery of thymopoiesis, as assessed by TI (B) and number of naive CD45RA+CD4+ T cells (C). (D) Spearman correlation demonstrates that the capacity to recover a broad TCR repertoire after transplant is dependent upon patient age.