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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.
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IMMUNOBIOLOGY
Most human thymic and peripheral-blood CD4+CD25+ regulatory T cells express 2 T-cell receptors
Heli Tuovinen,
Jukka T. Salminen, and
T. Petteri Arstila
From the Haartman Institute, Department of Immunology, University of Helsinki, Finland; and Department of Surgery, Hospital for Children and Adolescents, Helsinki University Hospital, Finland.
Lack of allelic exclusion in the T-cell receptor (TCR)  locus gives rise to 2 different TCRs in 10% to 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 2 distinct V chains and thus 2 TCRs at least 3 times as often as other T cells. Extrapolating from flow cytometric analysis using V2-, V12-, and V24-specific monoclonal antibodies (mAbs), we estimated that between 50% and 99% of the CD25+ Treg cells were dual specific, as compared with about 20% of their CD25– counterparts. Moreover, both TCRs were equally capable of transmitting signals upon ligation. Cells with 2 TCRs also expressed more FOXP3, the Treg-cell lineage specification factor, than cells with a single TCR. Our findings suggest that expression of 2 TCRs favors differentiation to the Treg-cell lineage in humans and raise the question of the potential functional consequences of dual specificity.
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