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J. Exp. Med., Volume 190, Number 4, August 16, 1999 479-486
Copyright © 1999 by The Rockefeller University Press.

Direct Evidence for Thymic Function in Adult Humans

Jean-François Poulina,b, Mohan N. Viswanathand, Jeffrey M. Harrisd, Krishna V. Komandurid,e, Eric Wiederd, Nancy Ringuettea, Morgan Jenkinsd, Joseph M. McCuned,f, and Rafick-Pierre Sékalya,b,c,g
a From the Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Quebec H2W 1R7, Canada
b Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada
c Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 1A3, Canada
d The Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, California 94141
e Division of Hematology and Oncology, Microbiology, and Immunology, University of California at San Francisco, San Francisco, California 94143
f Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, California 94143
g Département de Microbiologie et d'Immunologie, Université de Montréal, Montréal, Quebec H3C 3J7, Canada

Correspondence to: Rafick-Pierre Sékaly, Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Quebec H2W 1R7, Canada. Tel:514-987-5550 Fax:514-987-5711 E-mail:sekalyr{at}ircm.qc.ca.

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-ß 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 Vß 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.

Key Words: thymus, T cell receptor, deletion circles, naive T cells, immune reconstitution


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