Autor(es): Nunes-Cabaço, H. ; C Ribot, Julie ; Caramalho, Íris ; Serra-Caetano, Ana ; Silva-Santos, Bruno ; E Sousa, Ana
Data: 2010
Origem: Repositório da Universidade de Lisboa
Assunto(s): Foxp3; Human T-cell development; Murine T-cell development; Regulatory T cells; Thymus
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 TCRalpha-sufficient but not in TCRalpha-deficient animals, genetically showing the TCR dependence of Foxp3 expression at pre-DP stages of T-cell development.
