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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4063-4070. Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-04-016105. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-016105v1 108/13/4063    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuovinen, H. Articles by Arstila, T. P. Search for Related Content PubMed PubMed Citation Articles by Tuovinen, H. Articles by Arstila, T. P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 11, 2006 Accepted August 8, 2006 Most human thymic and peripheral blood CD4+CD25+ regulatory T cells express two T cell receptors Heli Tuovinen, Jukka Salminen, and T. Petteri Arstila* Haartman Institute, Department of Immunology, University of Helsinki, Finland Department of Surgery, Hospital for Children and Adolescents, Helsinki University Hospital, Helsinki * Corresponding author; email: petteri.arstila{at}helsinki.fi. Lack of allelic exclusion in the T cell receptor (TCR) locus gives rise to two different TCRs in 10-30% of all mature T cells, but the significance of such dual-specificity remains controversial. Here we show that human CD4+CD25+ regulatory T (Treg) cells express two distinct V chains and thus two TCRs at least three times as often as other T cells. Extrapolating from flow cytometric analysis using V2, V12, and V24-specific mAb we estimated that between 50% and 99% of the CD25+ Treg cells were dual-specific, as compared to about 20% of their CD25- counterparts. Moreover, both TCRs were equally capable of transmitting signals upon ligation. Cells with two TCRs also expressed more FOXP3, the Treg cell lineage specification factor, than cells with a single TCR. Our findings suggest that expression of two TCRs favors differentiation to the Treg cell lineage in humans and raise the question of the potential functional consequences of dual-specificity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. F. Campese, P. Grazioli, S. Colantoni, E. Anastasi, M. Mecarozzi, S. Checquolo, G. De Luca, D. Bellavia, L. Frati, A. Gulino, et al. Notch3 and pT{alpha}/pre-TCR sustain the in vivo function of naturally occurring regulatory T cells Int. Immunol., June 1, 2009; 21(6): 727 - 743. [Abstract] [Full Text] [PDF] G. Gong, L. Shao, Y. Wang, C. Y. Chen, D. Huang, S. Yao, X. Zhan, H. Sicard, R. Wang, and Z. W. Chen Phosphoantigen-activated V{gamma}2V{delta}2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection Blood, January 22, 2009; 113(4): 837 - 845. [Abstract] [Full Text] [PDF] A. Dolganiuc and G. Szabo T cells with regulatory activity in hepatitis C virus infection: what we know and what we don't J. Leukoc. Biol., September 1, 2008; 84(3): 614 - 622. [Abstract] [Full Text] [PDF] H. Tuovinen, E. Kekalainen, L. H. Rossi, J. Puntila, and T. Petteri Arstila Cutting Edge: Human CD4-CD8- Thymocytes Express FOXP3 in the Absence of a TCR J. Immunol., March 15, 2008; 180(6): 3651 - 3654. [Abstract] [Full Text] [PDF] J. Larkin III, A. L. Rankin, C. C. Picca, M. P. Riley, S. A. Jenks, A. J. Sant, and A. J. Caton CD4+CD25+ Regulatory T Cell Repertoire Formation Shaped by Differential Presentation of Peptides from a Self-Antigen J. Immunol., February 15, 2008; 180(4): 2149 - 2157. [Abstract] [Full Text] [PDF] N. Fazilleau, H. Bachelez, M.-L. Gougeon, and M. Viguier Cutting Edge: Size and Diversity of CD4+CD25high Foxp3+ Regulatory T Cell Repertoire in Humans: Evidence for Similarities and Partial Overlapping with CD4+CD25 T Cells J. Immunol., September 15, 2007; 179(6): 3412 - 3416. [Abstract] [Full Text] [PDF]

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