title: Interleukin-7 promotes human regulatory T cell development at the CD4+CD8+ double-positive thymocyte stage.
abstract: Although mature human FOXP3(+) regulatory T cells are CD127 (IL-7Rα) negative, CD4(+)CD8(+) FOXP3(+) thymocytes express relatively high levels of CD127 and are responsive to IL-7. However, the role of IL-7 in human regulatory T cell development is poorly known. We show that at the CD4(+)CD8(+) stage, FOXP3(+) thymocytes are highly susceptible to apoptosis, and IL-7 selectively rescues them from death, leading to an increased frequency of FOXP3(+) cells. IL-7 also promotes the development of regulatory T cell phenotype by inducing up-regulation of FOXP3(+) and CTLA-4 expression. In contrast, IL-7 does not enhance proliferation of FOXP3(+)thymocytes or induce demethylation of FOXP3(+) regulatory T cell-specific demethylated region. After the CD4(+)CD8(+) stage, the FOXP3(+) thymocytes down-regulate CD127 expression but despite very low levels of CD127, remain responsive to IL-7. These results suggest that IL-7 affects human regulatory T cell development in the thymus by at least 2 distinct mechanisms: suppression of apoptosis and up-regulation of FOXP3(+) expression.
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland; and anni.tuulasvaara@helsinki.fi.
authors.forename: Anni
authors.initials: A
authors.lastname: Tuulasvaara
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland; and.
authors.forename: Reetta
authors.initials: R
authors.lastname: Vanhanen
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland; and.
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Baldauf
authors.affiliation: Department of Surgery, Hospital for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Puntila
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland; and.
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000494:pharmacology*; D008297:Male; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain
keywords: apoptosis; cytokines; thymus