title: Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells.
abstract: Upon activation, naive CD4 T cells differentiate into a variety of T-helper-cell subsets characterized by different cytokine production and functions. Currently, lineage commitment is considered to depend mostly on the environmental context to which naive CD4 T cells are exposed. Here we challenge this model based on the supposed homogeneity of the naive CD4 T-cell compartment. We show that peripheral naive CD4 T cells can be subdivided into two subsets according to Ly-6C expression. Furthermore, the two newly defined subsets (Ly-6C(-) and Ly-6C(+) naive CD4 T cells) are not equal in their intrinsic ability to commit into the induced regulatory T-cell lineage. Finally, phenotypic analysis, imaging and adoptive transfer experiments reveal that Ly-6C expression is modulated by self-recognition, allowing the dichotomization of the naive CD4 T-cell compartment into two cell subsets with distinct self-reactivity. Altogether, our results show that naive CD4 T cells with the highest avidity for self are prone to differentiate into regulatory T cells.
authors.affiliation: CNRS UMR8104, Cochin Hospital, 75014 Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martin
authors.forename: Cédric
authors.initials: C
authors.lastname: Auffray
authors.forename: Arnaud
authors.initials: A
authors.lastname: Delpoux
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pommier
authors.forename: Aurélie
authors.initials: A
authors.lastname: Durand
authors.forename: Céline
authors.initials: C
authors.lastname: Charvet
authors.forename: Philippe
authors.initials: P
authors.lastname: Yakonowsky
authors.forename: Hubert
authors.initials: H
authors.lastname: de Boysson
authors.forename: Nelly
authors.initials: N
authors.lastname: Bonilla
authors.forename: Alexandra
authors.initials: A
authors.lastname: Audemard
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Benoit L
authors.initials: BL
authors.lastname: Salomon
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Bruno
authors.initials: B
authors.lastname: Lucas
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D005434:Flow Cytometry; D005453:Fluorescence; D051858:Forkhead Transcription Factors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D049452:Green Fluorescent Proteins