Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling threshold

Brenda M Rivera Reyes, Silvio Danese, Miquel Sans, Claudio Fiocchi, Alan D. Levine

Research output: Contribution to journalArticle

Abstract

Mucosal immune tolerance in the healthy intestine is typified by lamina propria T cell (LPT) functional hyporesponsiveness after TCR engagement when compared with peripheral blood T cell (PBT). When LPT from an inflamed intestine are activated through TCR cross-linking, their responsiveness is stronger. LPT are thus capable of switching from a tolerant to a reactive state, toggling between high and low thresholds of activation. We demonstrate that in normal LPT global tyrosine phosphorylation upon TCR cross-linking or an increase in intracellular H2O2, an inhibitor of protein tyrosine phosphatases, is muted. Thus, we propose that LPT have a greater reducing capacity than PBT, shifting the balance between kinases and protein tyrosine phosphatases in favor of the latter. Surface γ-glutamyl transpeptidase, an indirect indicator of redox potential, and glutathione are significantly elevated in LPT compared with PBT, suggesting that elevated glutathione detoxifies TCR-induced reactive oxygen species. When glutathione is depleted, TCR-induced LPT tyrosine phosphorylation rises to PBT levels. Conversely, increasing glutathione in PBT attenuates tyrosine phosphorylation. In LPT isolated from inflamed mucosa, TCR cross-linking induces greater phosphorylation, and γ-glutamyl transpeptidase levels are reduced compared with those from autologous noninflamed tissue. We conclude that the high TCR signaling threshold of mucosal T cells is tuned by intracellular redox equilibrium, whose dysregulation may mediate intestinal inflammation.

Original languageEnglish
Pages (from-to)2158-2166
Number of pages9
JournalJournal of Immunology
Volume175
Issue number4
Publication statusPublished - Aug 15 2005

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Oxidation-Reduction
T-Lymphocytes
Mucous Membrane
Blood Cells
Glutathione
Phosphorylation
Tyrosine
Protein Tyrosine Phosphatases
gamma-Glutamyltransferase
Intestines
Immune Tolerance
Reactive Oxygen Species
Phosphotransferases
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Reyes, B. M. R., Danese, S., Sans, M., Fiocchi, C., & Levine, A. D. (2005). Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling threshold. Journal of Immunology, 175(4), 2158-2166.

Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling threshold. / Reyes, Brenda M Rivera; Danese, Silvio; Sans, Miquel; Fiocchi, Claudio; Levine, Alan D.

In: Journal of Immunology, Vol. 175, No. 4, 15.08.2005, p. 2158-2166.

Research output: Contribution to journalArticle

Reyes, BMR, Danese, S, Sans, M, Fiocchi, C & Levine, AD 2005, 'Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling threshold', Journal of Immunology, vol. 175, no. 4, pp. 2158-2166.
Reyes, Brenda M Rivera ; Danese, Silvio ; Sans, Miquel ; Fiocchi, Claudio ; Levine, Alan D. / Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling threshold. In: Journal of Immunology. 2005 ; Vol. 175, No. 4. pp. 2158-2166.
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