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The cytokine interleukin (IL)-7 is essential for Treg-cell homeostasis. It remains unclear, however, whether IL-7 regulates the homeostatic fitness of T cells quantitatively and, if so, by what mechanisms. We addressed this question by analysing T cells exposed to different levels of IL-7 signalling in vivo. Using TCR transgenic mice that conditionally express IL-7Rα, we show that T-cell longevity in the absence of survival cues is not a cell-intrinsic property but rather a dynamic process of which IL-7 signalling is a key regulator. Naïve T cells deficient in IL-7Rα expression underwent rapid cell death within hours of in vitro culture. In contrast, the same T cells from lymphopenic hosts, in which IL-7 is non-limiting, were able to survive in culture independently of growth factors for many days. Surprisingly, different levels of IL-7 signalling in vivo evoked distinct molecular mechanisms to regulate homeostatic fitness. When IL-7 was non-limiting, increased survival was associated with up-regulation of anti-apoptotic Bcl2 family members. In contrast, in T-cell replete conditions i.e. when IL-7 is limiting, we found evidence that IL-7 regulated T-cell fitness by distinct non-transcriptional mechanisms. Together, these data demonstrate a quantitative aspect to IL-7 signalling dependent on distinct molecular mechanisms.

Original publication

DOI

10.1002/eji.201141514

Type

Journal article

Journal

European journal of immunology

Publication Date

12/2011

Volume

41

Pages

3656 - 3666

Addresses

Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.

Keywords

T-Lymphocytes, Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Receptors, Antigen, T-Cell, Receptors, Interleukin-7, Proto-Oncogene Proteins c-bcl-2, Interleukin-7, Signal Transduction, Apoptosis, Up-Regulation, Homeostasis