Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/121405
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | TRAF2 regulates peripheral CD8⁺ T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15 |
Other Titles: | TRAF2 regulates peripheral CD8(+) T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15 |
Author: | Villanueva, J.E. Malle, E.K. Gardam, S. Silveira, P.A. Zammit, N.W. Walters, S.N. Brink, R. Grey, S.T. |
Citation: | European Journal of Immunology, 2015; 45(6):1820-1831 |
Publisher: | Wiley |
Issue Date: | 2015 |
ISSN: | 0014-2980 1521-4141 |
Statement of Responsibility: | 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 TNF receptor (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. |
Keywords: | CD8+ T cell; homeostasis; IL‐15; NKT cell; TRAF2; TRAF3 |
Rights: | © 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim |
DOI: | 10.1002/eji.201445416 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/427649 |
Published version: | http://dx.doi.org/10.1002/eji.201445416 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.