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

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

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., Frommer, C., Stoycheva, D., Deiser, K., Kalinke, U., Blankenstein, T., Kammertoens, T., 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
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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