Modulation of human T-cell functions by reactive nitrogen species

Tihana Kasic, Piergiuseppe Colombo, Cristiana Soldani, Chiuhui M. Wang, Elena Miranda, Massimo Roncalli, Vincenzo Bronte, Antonella Viola

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have suggested that T-lymphocyte dysfunction might be attributable to nitrative stress induced by reactive nitrogen species (RNS). In this manuscript, we explored this hypothesis and provided a direct demonstration of the inhibitory effects of RNS on human T-cell signaling, activation, and migration. We found that short exposure of human T cells to RNS induced tyrosine phosphorylation of several proteins, including the CD3ζ chain of the TCR complex, and release of Ca2+ from intracellular stores. When the exposure to RNS was prolonged, T cells became refractory to stimulation, downregulated membrane receptors such as CD4, CD8, and chemokine receptors, and lost their ability to migrate in response to chemokines. Since substantial protein nitration, a hallmark of nitrative stress, was observed in various human cancers, intratumoral generation of RNS might represent a relevant mechanism for tumor evasion from immune surveillance.

Original languageEnglish
Pages (from-to)1843-1849
Number of pages7
JournalEuropean Journal of Immunology
Volume41
Issue number7
DOIs
Publication statusPublished - Jul 2011

Keywords

  • Reactive nitrogen species
  • T-cell activation
  • Tumor microenvironment

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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