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e-Article

Direct evidence for thymic function in adult humans.
Document Type
article
Source
The Journal of experimental medicine. 190(4)
Subject
Thymus Gland
T-Lymphocyte Subsets
Fetal Blood
Animals
Humans
Mice
L-Selectin
Receptors
Antigen
T-Cell
alpha-beta
Flow Cytometry
Sequence Deletion
Aging
Phenotype
Genes
T-Cell Receptor beta
Adult
Aged
Middle Aged
CD4 Antigens
Leukocyte Common Antigens
thymus
T cell receptor
deletion circles
naive T cells
immune reconstitution
Genes
T-Cell Receptor beta
Receptors
Antigen
T-Cell
alpha-beta
Medical and Health Sciences
Immunology
Language
Abstract
The understanding of human thymic function and evaluation of its contribution to T cell homeostasis are matters of great importance. Here we report the development of a novel assay to quantitate the frequency and diversity of recent thymic emigrants (RTEs) in the peripheral blood of humans. Such cells were defined by the presence of T cell receptor (TCR) rearrangement deletion circles (DCs), episomal byproducts of TCR-beta V(D)J rearrangement. DCs were detected in T cells in the thymus, cord blood, and adult peripheral blood. In the peripheral blood of adults aged 22 to 76 years, their frequency was highest in the CD4(+)CD45RA(+) CD62L(+) subpopulation of naive T cells. TCR DCs were also observed in other subpopulations of peripheral blood T cells, including those with the CD4(+)CD45RO(-)CD62L(+) and CD4(+)CD45RO(+)CD62L(+) phenotypes. RTEs were observed to have more than one Vbeta rearrangement, suggesting that replenishment of the repertoire in the adult is at least oligoclonal. These results demonstrate that the normal adult thymus continues to contribute, even in older individuals, a diverse set of new T cells to the peripheral circulation.