Interferon-γ Receptor Signaling in Dendritic Cells Restrains Spontaneous Proliferation of CD4 T Cells in Chronic Lymphopenic Mice.
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Dunay, Ildiko Rita
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AbstractIn 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.
CitationFront Immunol. 2019 Feb 7;10:140. doi: 10.3389/fimmu.2019.00140. eCollection 2019.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7,30625 Hannover, Germany.
JournalFrontiers in Immunology
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