Posttranscriptional Silencing of Effector Cytokine mRNA Underlies the Anergic Phenotype of Self-Reactive T Cells

Alejandro V. Villarino, Shoshana D. Katzman, Eugenio Gallo, Omer Miller, Shuwei Jiang, Michael T. McManus, Abul K. Abbas

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)50-60
Number of pages11
JournalImmunity
Volume34
Issue number1
DOIs
StatePublished - Jan 28 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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