Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells.

Fiche publication


Date publication

janvier 2013

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CHARVET Céline, Dr POMMIER Arnaud


Tous les auteurs :
Martin B, Auffray C, Delpoux A, Pommier A, Durand A, Charvet C, Yakonowsky P, de Boysson H, Bonilla N, Audemard A, Sparwasser T, Salomon BL, Malissen B, Lucas B

Résumé

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.

Mots clés

Adoptive Transfer, Animals, Antigens, Ly, metabolism, Cell Differentiation, immunology, Cell Polarity, immunology, Flow Cytometry, Fluorescence, Forkhead Transcription Factors, metabolism, Green Fluorescent Proteins, metabolism, Histocompatibility Antigens Class II, metabolism, Inflammatory Bowel Diseases, immunology, Mice, Mice, Inbred C57BL, T-Lymphocytes, Regulatory, cytology, Th17 Cells, cytology

Référence

Nat Commun. 2013 ;4:2209