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| Content Provider | frontiers |
|---|---|
| Author | Knop, Laura Frommer, Charlotte Stoycheva, Diana Deiser, Katrin Kalinke, Ulrich Blankenstein, Thomas Kammertoens, Thomas Dunay, Ildiko Rita Schüler, Thomas |
| 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. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2019.00140 |
| Volume Number | 10 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2019-02-07 |
| Access Restriction | Open |
| Subject Keyword | Lymphopenia CD4+ T cells Interferon-γ Lymphopenia-induced proliferation (LIP) Dendritic Cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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