Published 18 March 2002. doi:10.1084/jem.20011756
© Rockefeller University Press, 0022-1007/2002/3/789/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 6, March 18, 2002 789-794
Two Subsets of Naive T Helper Cells with Distinct T Cell Receptor Excision Circle Content in Human Adult Peripheral Blood
Sonja Kimmig1,
Grzegorz K. Przybylski2,
Christian A. Schmidt2,
Katja Laurisch2,
Beate Möwes1,
Andreas Radbruch1 and
Andreas Thiel1
1 Department of Clinical Immunology, Deutsches Rheuma-Forschungszentrum Berlin, 10117 Berlin, Germany
2 Department of Haematology und Oncology, Virchow Klinikum, Humboldt-Universität zu Berlin, 13353 Berlin, Germany
Address correspondence to Dr. Andreas Thiel, Clinical Immunology, DRFZ Berlin, Schumannstr. 21/22, 10117 Berlin, Germany. Phone: 49-30-28460-681; Fax: 49-30-28460-603; E-mail: thiel{at}drfz.de
During ageing thymic function declines and is unable to meet the demand for peripheral T helper (Th) cell replenishment. Therefore, population maintenance of naive Th cells must be at least partly peripherally based. Such peripheral postthymic expansion of recent thymic emigrants (RTEs) during ageing consequently should lead to loss or dilution of T cell receptor excision circles (TRECs) from a subset of naive T cells. We have identified two subsets of naive Th cells in human adult peripheral blood characterized by a striking unequal content of TRECs, indicating different peripheral proliferative histories. TRECs are highly enriched in peripheral naive CD45RA+ Th cells coexpressing CD31 compared with peripheral naive CD45RA+ Th cells lacking CD31 expression, in which TRECs can hardly be detected. Furthermore we show that CD31-CD45RA+ Th cells account for increasing percentages of the naive peripheral Th cell pool during ageing but retain phenotypic and functional features of naive Th cells. As CD31 is lost upon T cell receptor (TCR) engagement in vitro, we hypothesize that TCR triggering is a prerequisite for homeostatically driven peripheral postthymic expansion of human naive RTEs. We describe here the identification of peripherally expanded naive Th cells in human adult blood characterized by the loss of CD31 expression and a highly reduced TREC content.
Key Words: CD31 naive Th cells Th cell homeostasis recent thymic emigrants peripheral Th cell pool

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-
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-
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-
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-
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-
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[Abstract]
[Full Text]
-
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[Abstract]
[Full Text]
-
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[Abstract]
[Full Text]
-
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