Format

Send to

Choose Destination
J Immunol. 2009 Nov 15;183(10):6095-101. doi: 10.4049/jimmunol.0803510. Epub 2009 Oct 19.

Anergic T cells are metabolically anergic.

Author information

1
The Sidney-Kimmel Cancer Research Center, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.

Abstract

Full T cell activation requires TCR engagement (signal 1) in the context of costimulation (signal 2). Costimulation is required for maximal expression of effector cytokines and prevention of T cell anergy. It has become increasingly clear that another major function of costimulation is to up-regulate the metabolic machinery necessary for T cell function. In this report we demonstrate that anergic T cells are metabolically anergic, in that upon full stimulation (signals 1 plus 2) they fail to up-regulate the machinery necessary to support increased metabolism. These findings suggest that one mechanism responsible for the maintenance of T cell anergy is failure to up-regulate the metabolic machinery. Furthermore, we demonstrate that by blocking leucine, glucose, and energy metabolism, T cell activation is mitigated. Additionally, inhibition of these metabolic pathways during T cell activation leads to anergy in Th1-differentiated cells. Overall, our findings extend the role of T cell metabolism in regulating T cell function.

PMID:
19841171
PMCID:
PMC2884282
DOI:
10.4049/jimmunol.0803510
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center