Details

Autor(en) / Beteiligte

• Villanueva, Jeanette E
• Malle, Elisabeth K
• Gardam, Sandra
• Silveira, Pablo A
• Zammit, Nathan W
• Walters, Stacey N
• Brink, Robert
• Grey, Shane T

Titel

TRAF2 regulates peripheral CD8 super(+) T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15

Ist Teil von

• European journal of immunology, 2015-06, Vol.45 (6), p.1820-1831

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Wiley Online Library Database Model

Beschreibungen/Notizen

• In this study, a critical and novel role for TNF receptor (TNFR) associated factor 2 (TRAF2) is elucidated for peripheral CD8 super(+) 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 naive CD8 super(+) T-cell subsets. IL-15-dependent populations were reduced further, as TRAF2TKO mice displayed a marked 70% reduction in central memory CD8 super(+)CD44 super(hi)CD1 22 super(+) T cells and 80% decrease in NKT cells. TRAF2TKO CD8 super(+)CD44 super(hi) T cells exhibited impaired dose-dependent proliferation to exogenous IL-15. In contrast, TRAF2TKO CD8 super(+) T cells proliferated normally to anti-CD3 and TRAF2TKO CD8 super(+)CD44 super(hi) T cells exhibited normal proliferation to exogenous IL-2. TRAF2TKO CD8 super(+) 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 super(+)CD44 super(hi)CD1 22 super(+) and NKT cells was mechanistically linked to an inability to respond to IL-15. The reduced CD8 super(+)CD44 super(hi)CD1 22 super(+) T-cell and NKT-cell populations in TRAF2TKO mice were rescued in the presence of high dose IL-15 by IL-15/IL-15R alpha complex administration. These studies demonstrate a critical role for TRAF2 in the maintenance of peripheral CD8 super(+) CD44 super(hi)CD122 super(+) T-cell and NKT-cell homeostasis by modulating sensitivity to T-cell intrinsic growth factors such as IL-15.