Multiparameter grouping delineates heterogeneous populations of human IL-17 and/or IL-22 T-cell producers that share antigen specificities with other T-cell subsets

Authors

  • Martin Larsen,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
    2. Université Pierre et Marie Curie-Paris 6, Paris, France
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    • These authors contributed equally to this work.

  • Laurent Arnaud,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
    2. Service de médecine interne 2, C.H.U. Pitié-Salpêtrière, Paris, France
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    • These authors contributed equally to this work.

  • Miguel Hié,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
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    • These authors contributed equally to this work.

  • Christophe Parizot,

    1. Laboratoire AP-HP d'Immunologie Cellulaire et Tissulaire, Paris, France
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  • Karim Dorgham,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
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  • Mohamed Shoukry,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
    2. Laboratoire AP-HP d'Immunologie Cellulaire et Tissulaire, Paris, France
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  • Mathilde Kemula,

    1. Département de Dermatologie, AP-HP, Hôpital Tenon, Paris, France
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  • Stéphane Barete,

    1. Université Pierre et Marie Curie-Paris 6, Paris, France
    2. Département de Dermatologie, AP-HP, Hôpital Tenon, Paris, France
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  • David Derai,

    1. Laboratoire AP-HP d'Immunologie Cellulaire et Tissulaire, Paris, France
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  • Delphine Sauce,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
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  • Zahir Amoura,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
    2. Service de médecine interne 2, C.H.U. Pitié-Salpêtrière, Paris, France
    3. Université Pierre et Marie Curie-Paris 6, Paris, France
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  • Jérôme Pène,

    1. Inserm Unité 844, Montpellier, France
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  • Hans Yssel,

    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
    2. Inserm Unité 844, Montpellier, France
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  • Guy Gorochov

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale (Inserm) UMR-S, Paris, France
    2. Laboratoire AP-HP d'Immunologie Cellulaire et Tissulaire, Paris, France
    3. Université Pierre et Marie Curie-Paris 6, Paris, France
    • Immunologie cellulaire et tissulaire, UMR-S 945, Hôpital Pitié-Salpêtrière, 83 bd. De l'Hôpital, 75013 Paris, France Fax: +33-1-42-17-74-90
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Abstract

The ontogenic relationship between pro-inflammatory populations of interleukin-17 (IL-17A)- and/or IL-22-producing T cells and other T-cell subsets is currently unclear in humans. To appreciate T helper cell-lineage commitment, we combined cytokine production profiles of in vitro expanded T-cell clones with T-cell receptor (TCR) clonotypic signatures. Moreover, ex vivo cytokine production profiles at the single-cell level were analyzed using an original approach based on the hierarchical cluster analysis of multiparametric flow cytometry data. These combined approaches enabled the delineation of distinct functional T-cell subsets, including Th1, Th2, Tr1, Th17 cells and a highly polyfunctional IL-22-producing T-cell population. Cluster analysis highlighted that the IL-22-producing T-cell population should be considered independently from the Th17 and Th1 subsets, although it was more closely related to the former. In parallel, we observed extensive TCRαβ sharing across all five subsets defined. The strategy described here allows the objective definition of cellular subsets and an unbiased insight into their similarities. Together, our results underscore the ontogenic plasticity of CD4+ T-cell progenitors, which can adopt a differentiation profile irrespective of antigen specificity.

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