Foxp3 induction in human and murine thymus precedes the CD4+ CD8+ stage but requires early T-cell receptor expression.
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.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Helena
H
Nunes-Cabaço
Julie C
JC
Ribot
Iris
I
Caramalho
Ana
A
Serra-Caetano
Bruno
B
Silva-Santos
Ana E
AE
Sousa
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell