Title |
TRAF2 regulates peripheral CD8+ T‐cell and NKT‐cell homeostasis by modulating sensitivity to IL‐15
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Published in |
European Journal of Immunology, May 2015
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DOI | 10.1002/eji.201445416 |
Pubmed ID | |
Authors |
Jeanette E Villanueva, Elisabeth K Malle, Sandra Gardam, Pablo A Silveira, Nathan W Zammit, Stacey N Walters, Robert Brink, Shane T Grey |
Abstract |
In this study, a critical and novel role for TNFR-associated factor 2 (TRAF2) is elucidated for peripheral CD8(+) T-cell and NKT-cell homeostasis. Mice deficient in TRAF2 only in their T cells (TRAF2TKO) show ∼40% reduction in effector-memory and ∼50% reduction in naïve CD8(+) T-cell subsets. IL-15-dependent populations were reduced further, as TRAF2TKO mice displayed a marked ∼70% reduction in central-memory CD8(+) CD44(hi) CD122(+) T cells and ∼80% decrease in NKT cells. TRAF2TKO CD8(+) CD44(hi) T cells exhibited impaired dose-dependent proliferation to exogenous IL-15. In contrast, TRAF2TKO CD8(+) T cells proliferated normally to anti-CD3 and TRAF2TKO CD8(+) CD44(hi) T cells exhibited normal proliferation to exogenous IL-2. TRAF2TKO CD8(+) T cells expressed normal levels of IL-15 associated receptors and possessed functional IL-15 mediated STAT5 phosphorylation, however TRAF2 deletion caused increased AKT activation. Loss of CD8(+) CD44(hi) CD122(+) and NKT cells was mechanistically linked to an inability to respond to IL-15. The reduced CD8(+) CD44(hi) CD122(+) T-cell and NKT-cell populations in TRAF2TKO mice were rescued in the presence of high dose IL-15 by IL-15/IL-15Rα complex administration. These studies demonstrate a critical role for TRAF2 in the maintenance of peripheral CD8(+) CD44(hi) CD122(+) T-cell and NKT-cell homeostasis by modulating sensitivity to T-cell intrinsic growth factors such as IL-15 This article is protected by copyright. All rights reserved. |
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Mendeley readers
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Unknown | 12 | 100% |
Demographic breakdown
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Student > Ph. D. Student | 5 | 42% |
Other | 1 | 8% |
Student > Doctoral Student | 1 | 8% |
Student > Master | 1 | 8% |
Researcher | 1 | 8% |
Other | 1 | 8% |
Unknown | 2 | 17% |
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Immunology and Microbiology | 3 | 25% |
Biochemistry, Genetics and Molecular Biology | 2 | 17% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
Neuroscience | 1 | 8% |
Other | 0 | 0% |
Unknown | 2 | 17% |