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Updated: Jul 20, 2026
Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Most human thymic and peripheral-blood CD4+ CD25+ regulatory T cells express 2 T-cell receptors
Heli Tuovinen1, Jukka T Salminen, T Petteri Arstila
1Haartman Institute, Department of Immunology, PB21, 00014 University of Helsinki, Finland.
Lack of allelic exclusion in the T-cell receptor (TCR) alpha 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 Valpha chains and thus 2 TCRs at least 3 times as often as other T cells. Extrapolating from flow cytometric analysis using Valpha2-, Valpha12-, and Valpha24-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.
Lack of allelic exclusion in the T-cell receptor (TCR) alpha 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 Valpha chains and thus 2 TCRs at least 3 times as often as other T cells. Extrapolating from flow cytometric analysis using Valpha2-, Valpha12-, and Valpha24-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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