Format

Send to

Choose Destination
See comment in PubMed Commons below
Immunity. 2011 Jan 28;34(1):50-60. doi: 10.1016/j.immuni.2010.12.014. Epub 2011 Jan 13.

Posttranscriptional silencing of effector cytokine mRNA underlies the anergic phenotype of self-reactive T cells.

Author information

1
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.

Abstract

Self-reactive T cell clones that escape negative selection are either deleted or rendered functionally unresponsive (anergic), thus preventing them from propagating host tissue damage. By using an in vivo model, we investigated molecular mechanisms for T cell tolerance, finding that despite a characteristic inability to generate effector cytokine proteins, self-reactive T cells express large amounts of cytokine mRNAs. This disconnect between cytokine message and protein was not observed in T cells mounting productive responses to foreign antigens but, instead, was seen only in those responding to self, where the block in protein translation was shown to involve conserved AU-rich elements within cytokine 3'UTRs. These studies reveal that translation of abundant cytokine mRNAs is limited in self-reactive T cells and, thus, identify posttranscriptional silencing of antigen-driven gene expression as a key mechanism underlying the anergic phenotype of self-reactive T cells.

PMID:
21236706
PMCID:
PMC3955755
DOI:
10.1016/j.immuni.2010.12.014
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center