Interferon-? Receptor Signaling in Dendritic Cells Restrains Spontaneous Proliferation of CD4⁺ T Cells in Chronic Lymphopenic Mice.

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-? receptor (IFN-?R) expression, a process, which is promoted by the autocrine action of T cell-derived IFN-?. 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-?R 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-?R⁺ DCs, and T cell-derived IFN-?.

SUBMITTER: Knop L 

PROVIDER: S-EPMC6374634 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature