| First Author | Pearson C | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 12 | Pages | 3656-66 |
| PubMed ID | 21932447 | Mgi Jnum | J:179508 |
| Mgi Id | MGI:5302590 | Doi | 10.1002/eji.201141514 |
| Citation | Pearson C, et al. (2011) IL-7 determines the homeostatic fitness of T cells by distinct mechanisms at different signalling thresholds in vivo. Eur J Immunol 41(12):3656-66 |
| abstractText | 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-7Ralpha, 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. Naive T cells deficient in IL-7Ralpha 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. |
