title: Critical influence of the thymus on peripheral T cell homeostasis.
abstract: A tight balance between regulatory CD4+Foxp3+(Treg) and conventional CD4+Foxp3-(Tconv) T cell subsets in the peripheral compartment, maintained stable throughout most of lifetime, is essential for preserving self-tolerance along with efficient immune responses. An excess of Treg cells, described for aged individuals, may critically contribute to their reported immunodeficiency. In this work, we investigated if quantitative changes in thymus emigration may alter the Treg/Tconv homeostasis regardless of the aging status of the peripheral compartment.
  
  
  
  We used two different protocols to modify the rate of thymus emigration: thymectomy of adult young (4-6 weeks old) mice and grafting of young thymus onto aged (18 months old) hosts. Additionally, lymphoid cells from young and aged B6 mice were intravenously transferred to B6.RAG2-/-mice. Alterations in Treg and Tconv peripheral frequencies following these protocols were investigated after 30 days by flow cytometry.
  
  
  
  Thymectomized young mice presented a progressive increase in the Treg cell frequency, while the grafting of a functional thymus in aged mice restored the young-like physiological Treg/Tconv proportion. Strikingly, T cells derived from young or aged splenocytes colonized the lymphopenic periphery of RAG-/-hosts to the same extent, giving rise to similarly elevated Treg cell levels irrespective of the age of the donor population. In the absence of thymus output, the Treg subset seems to survive longer, as confirmed by their lower proportion of Annexin-V+cells.
  
  
  
  Our data suggest that the thymus-emigrating population, harboring an adequate proportion of Treg/Tconv lymphocytes, may be essential to keep the Treg cell balance, independently of age-related shifts intrinsic to the peripheral environment or to the T cell biology.
authors.affiliation: Departamento de ImunologiaInstituto de Microbiologia Paulo de Goés (IMPG)-Universidade Federal do Rio de JaneiroRio de Janeiro-RJBrazil; Departamento de ImunobiologiaInstituto de Biologia-Universidade Federal FluminenseNiterói-RJBrazil.
authors.forename: Pedro Henrique Oliveira
authors.initials: PH
authors.lastname: Vianna
authors.affiliation: Departamento de ImunologiaInstituto de Microbiologia Paulo de Goés (IMPG)-Universidade Federal do Rio de JaneiroRio de Janeiro-RJBrazil; Departamento de ImunobiologiaInstituto de Biologia-Universidade Federal FluminenseNiterói-RJBrazil.
authors.forename: Fábio B
authors.initials: FB
authors.lastname: Canto
authors.affiliation: Departamento de ImunologiaInstituto de Microbiologia Paulo de Goés (IMPG)-Universidade Federal do Rio de JaneiroRio de Janeiro-RJBrazil; Departamento de ImunobiologiaInstituto de Biologia-Universidade Federal FluminenseNiterói-RJBrazil.
authors.forename: Jeane S
authors.initials: JS
authors.lastname: Nogueira
authors.affiliation: Departamento de ImunologiaInstituto de Microbiologia Paulo de Goés (IMPG)-Universidade Federal do Rio de JaneiroRio de Janeiro-RJBrazil; Departamento de ImunobiologiaInstituto de Biologia-Universidade Federal FluminenseNiterói-RJBrazil.
authors.forename: Caroline Fraga Cabral Gomes
authors.initials: CF
authors.lastname: Nunes
authors.affiliation: Programa FIOCANCER VPPLR-Instituto Oswaldo Cruz-FIOCRUZ Rio de Janeiro-RJ Brazil.
authors.forename: Adriana César
authors.initials: AC
authors.lastname: Bonomo
authors.affiliation: Departamento de Imunobiologia Instituto de Biologia-Universidade Federal Fluminense Niterói-RJ Brazil.
authors.forename: Rita
authors.initials: R
authors.lastname: Fucs
mesh_terms: D000818:Animals; D006706:Homeostasis; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017634:Self Tolerance; D016176:T-Lymphocyte Subsets; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*
keywords: Peripheral T cell homeostasis; regulatory T cells; thymic output