Cutting Edge: Human CD4 super(-)CD8 super(-) Thymocytes Express FOXP3 in the Absence of a TCR

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 T...

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Published in:The Journal of immunology (1950) 2008-03, Vol.180 (6), p.3651-3654
Main Authors: Tuovinen, Heli, Kekaelaeinen, Eliisa, Rossi, Laura H, Puntila, Juha, Petteri Arstila, T
Format: Article
Language:English
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Summary: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 super(-)CD8 super(-) thymocytes in healthy humans express FOXP3, two thirds of them without any detectable alpha beta TCR. These TCR super(-)FOXP3 super(+) cells were mostly CD25 super(-) and did not express gamma delta TCR or B cell, NK cell, or monocyte-associated markers. Like mature Treg cells, they were mostly CD2 super(+)CD127 super(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.
ISSN:0022-1767