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Foxp3 induction in human and murine thymus precedes the CD4 + CD8 + stage but requires early T‐cell receptor expression
Author(s) -
NunesCabaço Helena,
Ribot Julie C,
Caramalho Íris,
SerraCaetano Ana,
SilvaSantos Bruno,
Sousa Ana E
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2010.4
Subject(s) - thymocyte , foxp3 , t cell receptor , cd8 , biology , t cell , transcription factor , microbiology and biotechnology , cd3 , receptor , immune system , immunology , gene , genetics
The thymus generates a T‐cell lineage dedicated to immune regulation, ‘naturally occurring’ regulatory T cells, best specified by the forkhead family transcription factor Foxp3. Here, we have conducted a parallel study in humans and mice where we have dissected the earliest stages of Foxp3 induction during thymocyte development. By analyzing a large collection of 21 human thymuses we show that Foxp3 can be consistently detected in CD4 immature single positive thymocytes that precede the CD4( + )CD8( + ) (double positive, DP) stage. The reduced levels of CD3 expression found at this stage of human thymocyte development raise the question of TCR (T‐cell receptor) requirement for Foxp3 induction. We further show that, in mice, Foxp3 expression was also detected in pre‐DP thymocytes of TCRα‐sufficient but not in TCRα‐deficient animals, genetically showing the TCR dependence of Foxp3 expression at pre‐DP stages of T‐cell development.