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Interferon-γ receptor signaling in dendritic cells restrains spontaneous proliferation of CD4(+) T cells in chronic lymphopenic mice

Authors

  • L. Knop
  • C. Frommer
  • D. Stoycheva
  • K. Deiser
  • U. Kalinke
  • T. Blankenstein
  • T. Kammertoens
  • I.R. Dunay
  • T. Schüler

Journal

  • Frontiers in Immunology

Citation

  • Front Immunol 10: 140

Abstract

  • In lymphopenic mice, T cells become activated and undergo lymphopenia-induced proliferation (LIP). However, not all T cells are equally sensitive to lymphopenia. Several lymphopenia-insensitive T cell clones were described and their non-responsiveness was mainly attributed to clone-specific properties. Here, we provide evidence for an additional, host-dependent mechanism restraining LIP of lymphopenia-insensitive CD4(+) T cells. We show that such cells undergo LIP in lymphopenic mice lacking IFN-γ receptor (IFN-γR) expression, a process, which is promoted by the autocrine action of T cell-derived IFN-γ. Additionally, LIP of lymphopenia-insensitive CD4(+) T cells requires an intact microflora and is accompanied by the massive accumulation of IL-6 and dendritic cells (DCs). Consistent with these results, IL-6 neutralization and the DC-specific restoration of IFN-γR expression are both sufficient to restrict LIP. Hence, the insensitivity of CD4(+) T cells to lymphopenia relies on cell-intrinsic properties and a complex interplay between the commensal microflora, IL-6, IFN-γR(+) DCs, and T cell-derived IFN-γ.


DOI

doi:10.3389/fimmu.2019.00140