IL‐7 derived from lymph node fibroblastic reticular cells is dispensable for naive T cell homeostasis but crucial for central memory T cell survival

The survival of peripheral T cells is dependent on their access to peripheral LNs (pLNs) and stimulation by IL‐7. In pLNs fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) produce IL‐7 suggesting their contribution to the IL‐7‐dependent survival of T cells. However, IL‐7 pro...

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Bibliographic Details
Published in:European journal of immunology 2020-06, Vol.50 (6), p.846-857
Main Authors: Knop, Laura, Deiser, Katrin, Bank, Ute, Witte, Amelie, Mohr, Juliane, Philipsen, Lars, Fehling, Hans J., Müller, Andreas J., Kalinke, Ulrich, Schüler, Thomas
Format: Article
Language:English
Subjects:
Animals
Cell Survival
central memory T cells
Endothelial cells
fibroblastic reticular cells
Fibroblasts - cytology
Fibroblasts - immunology
Homeostasis
IL‐7
Immunologic Memory
Immunological memory
Interleukin 7
Interleukin-7 - genetics
Interleukin-7 - immunology
Lymph nodes
Lymph Nodes - cytology
Lymph Nodes - immunology
Lymphocytes
Lymphocytes T
Memory cells
Mice
Mice, Knockout
naive T cells
Spleen
T cell homeostasis
T-Lymphocytes - cytology
T-Lymphocytes - immunology
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Summary:The survival of peripheral T cells is dependent on their access to peripheral LNs (pLNs) and stimulation by IL‐7. In pLNs fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) produce IL‐7 suggesting their contribution to the IL‐7‐dependent survival of T cells. However, IL‐7 production is detectable in multiple organs and is not restricted to pLNs. This raises the question whether pLN‐derived IL‐7 is required for the maintenance of peripheral T cell homeostasis. Here, we show that numbers of naive T cells (TN) remain unaffected in pLNs and spleen of mice lacking Il7 gene activity in pLN FRCs, LECs, or both. In contrast, frequencies of central memory T cells (TCM) are reduced in FRC‐specific IL‐7 KO mice. Thus, steady state IL‐7 production by pLN FRCs is critical for the maintenance of TCM, but not TN, indicating that both T cell subsets colonize different ecological niches in vivo. In peripheral LNs (pLNs) fibroblastic reticular cells (FRCs) are a major source of IL‐7, which is crucial for the maintenance of peripheral T cell homeostasis. Using FRC‐specific IL‐7 KO mice (FRCΔIL‐7), we demonstrate differential IL‐7 requirements for naive (TN) and central memory T cells (TCM).
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201948368