TY - JOUR
T1 - Age-dependent incidence, time course, and consequences of thymic renewal in adults
AU - Hakim, Frances T.
AU - Memon, Sarfraz A.
AU - Cepeda, Rosemarie
AU - Jones, Elizabeth C.
AU - Chow, Catherine K.
AU - Kasten-Sportes, Claude
AU - Odom, Jeanne
AU - Vance, Barbara A.
AU - Christensen, Barbara L.
AU - Mackall, Crystal L.
AU - Gress, Ronald E.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI200522492
DO - 10.1172/JCI200522492
M3 - Article
C2 - 15776111
AN - SCOPUS:20144387499
SN - 0021-9738
VL - 115
SP - 930
EP - 939
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -