Most human thymic and peripheral-blood CD4+ CD25+ regulatory T cells express 2 T-cell receptors.
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.
Tuovinen
Heli
H
Haartman Institute, Department of Immunology, PB21, 00014 University of Helsinki, Finland.
Salminen
Jukka T
JT
Arstila
T Petteri
TP
D000328:Adult; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016693:Receptors, Antigen, T-Cell, alpha-beta