Abstract
Interleukin 7 is essential for the survival of naive T lymphocytes. Despite its importance, its cellular source in the periphery remains poorly defined. Here we report a critical function for lymph node access in T cell homeostasis and identify T zone fibroblastic reticular cells in these organs as the main source of interleukin 7. In vitro, T zone fibroblastic reticular cells were able to prevent the death of naive T lymphocytes but not of B lymphocytes by secreting interleukin 7 and the CCR7 ligand CCL19. Using gene-targeted mice, we demonstrate a nonredundant function for CCL19 in T cell homeostasis. Our data suggest that lymph nodes and T zone fibroblastic reticular cells have a key function in naive CD4+ and CD8+ T cell homeostasis by providing a limited reservoir of survival factors.
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Acknowledgements
We thank M. Ansel, S. Bell, M. Charmoy, T. Andresen, P. Hyman, N. Killeen and J. Smith-Clerc for technical help; H. Robson MacDonald for critical reading of the manuscript; M. Cooper, W. van Ewijk, A. Farr, G. Gabbiani, B. Imhof, C. Ruegg and A. Wilson for antibodies; and N. Killeen for embryonic stem cells. Supported by the Swiss National Science Foundation (PPOOA-68805 to S.A.L.), the Boehringer Ingelheim Fonds (T.K.V.), the Swiss National Science Foundation (3100A0-102150/1 and 3100A0-113733/1 to B.H.) and the National Institutes of Health (AI45073 to J.G.C.).
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A.L. did the in vivo experiments, with assistance from M.R.B. and S.F., as well as all the in vitro assays, flow cytometry sorting and analysis, and in situ hybridization, and contributed to the writing of the manuscript; T.K.V. did the wrinkling assays in collaboration with B.H. and did the RT-PCR and assisted with the flow cytometry sorting and analysis; S.F. did most of the immunofluorescence with assistance from T.K.V.; H.A.-O. provided antibodies; S.A.L. generated the CCL19-deficient mice in the laboratory of J.G.C.; S.A.L. directed the study and wrote the manuscript; and all authors critically reviewed the manuscript.
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Link, A., Vogt, T., Favre, S. et al. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat Immunol 8, 1255–1265 (2007). https://doi.org/10.1038/ni1513
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DOI: https://doi.org/10.1038/ni1513
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