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

2005; American Society for Clinical Investigation; Volume: 115; Issue: 4 Linguagem: Inglês

10.1172/jci22492

1558-8238

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

Immunotherapy and Immune Responses

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 Vbeta 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.