Foxp3+ regulatory T cells promiscuously accept thymic signals critical for their development.
Foxp3(+) regulatory T cells develop in the thymus and are essential for maintaining peripheral tolerance to self tissues. We report the critical requirement for CD154 up-regulation specifically on, and during the thymic development of, Foxp3(+) regulatory T cells for the induction of their clonal expansion within the medulla. In the absence of this signal, there was a severe reduction in their thymic generation and output, leading to decreased peripheral numbers. Importantly, CD40 expression on either thymic dendritic or epithelial cells was sufficient to promote the development of normal numbers of Foxp3(+) regulatory T cells. This work suggests that CD154-transduced signals promote Foxp3(+) regulatory T cell development and highlights the plasticity of the thymic stroma for supporting their generation. Crucially, this study demonstrates that Foxp3(+) regulatory T cells can promiscuously accept a single critical signal necessary for their thymic development from different cellular sources, redefining our understanding of their generation.
Spence
Philip J
PJ
Department of Pathology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
Green
E Allison
EA
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D023201:CD40 Ligand