T cell anergy is reversed by active Ras and regulated by diacylglycerol kinase
US7381401B2 · kind B2 · utility
Assignee
Inventor
Key dates
| Filing date | Jan 10, 2005 |
| Grant date | Jun 3, 2008 |
| Priority date | — |
| Expiry date | Jan 26, 2025 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12Q1/485
- WIPO fieldMeasurement
- WIPO sectorInstruments
Abstract
T cell anergy has been correlated with defective Ras signaling. However, neither a causal relationship nor the mechanism of Ras hypoactivation have been established. Using adenoviral transduction of CAR Tg T cells to enable genetic manipulation in nonproliferating cells, we show that Ras61L restores IL-2 production and MAP kinase signaling in T cells anergized in vitro or in vivo. A gene array screen revealed upregulated diacylglycerol kinase (DGK) in the anergic state, which was confirmed by RT-PCR and Western blot analysis. A DGK inhibitor significantly restored IL-2 production by anergic cells. Our data support a causal role for DGK and defective Ras signaling in T cell anergy.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.