title: IL-2 prevents deletion of developing T-regulatory cells in the thymus.
abstract: In the thymus, strongly self-reactive T cells may undergo apoptotic deletion or differentiate into Foxp3+ T-regulatory (T-reg) cells. Mechanisms that partition T cells into these two fates are unclear. Here, we show that IL-2 signalling is required to prevent deletion of CD4+ CD8- CCR7+ Helios+ thymocytes poised to upregulate Foxp3. The deletion prevented by IL-2 signalling is Foxp3 independent and occurs later in thymocyte development than the deletion that is prevented by Card11 signalling. Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second.
authors.affiliation: Immunology Department, The John Curtin School of Medical Research, The Australian National University, Canberra 0200, Australia.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Hu
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Rushika C
authors.initials: RC
authors.lastname: Wirasinha
authors.affiliation: Immunology Department, The John Curtin School of Medical Research, The Australian National University, Canberra 0200, Australia.|Immunology Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.affiliation: Immunology Department, The John Curtin School of Medical Research, The Australian National University, Canberra 0200, Australia.|Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Daley
mesh_terms: D000818:Animals; D017209:Apoptosis; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2