title: Cutting edge: human CD4-CD8- thymocytes express FOXP3 in the absence of a TCR.
abstract: The best candidate for regulatory T (Treg) cell lineage-determining factor is currently the Forkhead box transcription factor FOXP3. FOXP3 up-regulation has been linked to TCR-mediated signals, and in mice the abrogation of TCR expression or signals also prevents FoxP3 expression. In contrast, the TCR dependence of human FOXP3 is assumed but not established. In this study we show on a single cell level that 1.4% (range 0.1-3.8%) of CD4(-)CD8(-) thymocytes in healthy humans express FOXP3, two thirds of them without any detectable alphabeta TCR. These TCR(-)FOXP3(+) cells were mostly CD25(-) and did not express gammadelta TCR or B cell, NK cell, or monocyte-associated markers. Like mature Treg cells, they were mostly CD2(+)CD127(low) and expressed cytoplasmic CTLA-4. Our results suggest that in immature human thymocytes the expression of FOXP3 precedes surface TCR, in which case TCR-mediated signals cannot be responsible for the thymic up-regulation of FOXP3.
authors.affiliation: Haartman Institute, Department of Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Tuovinen
authors.forename: Eliisa
authors.initials: E
authors.lastname: Kekäläinen
authors.forename: Laura H
authors.initials: LH
authors.lastname: Rossi
authors.forename: Juha
authors.initials: J
authors.lastname: Puntila
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011948:Receptors, Antigen, T-Cell