title: Modulation of human T-cell functions by reactive nitrogen species.
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.
authors.affiliation: Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: Tihana
authors.initials: T
authors.lastname: Kasic
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Colombo
authors.forename: Cristiana
authors.initials: C
authors.lastname: Soldani
authors.forename: Chiuhui M
authors.initials: CM
authors.lastname: Wang
authors.forename: Elena
authors.initials: E
authors.lastname: Miranda
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D026361:Reactive Nitrogen Species / Q000378:metabolism* / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D026361:Reactive Nitrogen Species; D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine; D030421:Peroxynitrous Acid; D002118:Calcium