title: Follicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells.
abstract: T follicular regulatory (Tfr) cells are a subset of Foxp3(+) regulatory T (Treg) cells that form in response to immunization or infection, which localize to the germinal centre where they control the magnitude of the response. Despite an increased interest in the role of Tfr cells in humoral immunity, many fundamental aspects of their biology remain unknown, including whether they recognize self- or foreign antigen. Here we show that Tfr cells can be specific for the immunizing antigen, irrespective of whether it is a self- or foreign antigen. We show that, in addition to developing from thymic derived Treg cells, Tfr cells can also arise from Foxp3(-) precursors in a PD-L1-dependent manner, if the adjuvant used is one that supports T-cell plasticity. These findings have important implications for Tfr cell biology and for improving vaccine efficacy by formulating vaccines that modify the Tfr:Tfh cell ratio.
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale, U1043, Toulouse F-31300, France.|Centre National de la Recherche Scientifique, U5282, Toulouse F-31300, France.|Université de Toulouse, Université Paul Sabatier, Toulouse F-31300, France.
authors.forename: Meryem
authors.initials: M
authors.lastname: Aloulou
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Carr
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale, U1043, Toulouse F-31300, France.|Centre National de la Recherche Scientifique, U5282, Toulouse F-31300, France.|Université de Toulouse, Université Paul Sabatier, Toulouse F-31300, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Gador
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bignon
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale, U1043, Toulouse F-31300, France.|Centre National de la Recherche Scientifique, U5282, Toulouse F-31300, France.|Université de Toulouse, Université Paul Sabatier, Toulouse F-31300, France.
authors.forename: Roland S
authors.initials: RS
authors.lastname: Liblau
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale, U1043, Toulouse F-31300, France.|Centre National de la Recherche Scientifique, U5282, Toulouse F-31300, France.|Université de Toulouse, Université Paul Sabatier, Toulouse F-31300, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fazilleau
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Linterman
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism; D005260:Female; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse
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