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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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