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

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Item Type:Article
Title:Interferon-γ receptor signaling in dendritic cells restrains spontaneous proliferation of CD4(+) T cells in chronic lymphopenic mice
Creators Name:Knop, L. and Frommer, C. and Stoycheva, D. and Deiser, K. and Kalinke, U. and Blankenstein, T. and Kammertoens, T. and Dunay, I.R. and Schüler, T.
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.
Keywords:CD4(+) T Cells, Interferon-γ, Lymphopenia, Lymphopenia-Induced Proliferation (LIP), Dendritic Cells, Animals, Mice
Source:Frontiers in Immunology
ISSN:1664-3224
Publisher:Frontiers Media SA (Switzerland)
Volume:10
Page Range:140
Date:7 February 2019
Official Publication:https://doi.org/10.3389/fimmu.2019.00140
PubMed:View item in PubMed

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