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Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes

Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low proliferative potential both in vivo and in vitro. Here, we have identified that the capacity of antigen-presenting cells to release cysteine upon receptor–ligand interactions represents a critical parameter for proliferation of LP-...

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Autores principales: Sido, Bernd, Braunstein, Jutta, Breitkreutz, Raoul, Herfarth, Christian, Meuer, Stefan C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193281/
https://www.ncbi.nlm.nih.gov/pubmed/10993921
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author Sido, Bernd
Braunstein, Jutta
Breitkreutz, Raoul
Herfarth, Christian
Meuer, Stefan C.
author_facet Sido, Bernd
Braunstein, Jutta
Breitkreutz, Raoul
Herfarth, Christian
Meuer, Stefan C.
author_sort Sido, Bernd
collection PubMed
description Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low proliferative potential both in vivo and in vitro. Here, we have identified that the capacity of antigen-presenting cells to release cysteine upon receptor–ligand interactions represents a critical parameter for proliferation of LP-Ts. The availability of cysteine is limiting for the intracellular production of glutathione, which in turn is essential for cell cycle progression. When cysteine is provided either directly or by addition of the reducing agent 2-mercaptoethanol to cystine-containing culture medium, proliferation of LP-T is fully restored. Importantly, coculture with peripheral blood monocytes that easily take up cystine, reduce cystine, and secrete cysteine also restores reactivity of LP-Ts to T cell receptor/CD3 stimulation. In marked contrast, lamina propria macrophages lack this capacity to elaborate cysteine, and thereby secure physiological unresponsiveness to antigen exposure in the intestinal microenvironment. The well-documented local recruitment of blood monocytes in inflammatory bowel disease (IBD) may thus represent an important parameter underlying hyperresponsiveness of T cells, an essential component of the pathogenesis of IBD.
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spelling pubmed-21932812008-04-16 Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes Sido, Bernd Braunstein, Jutta Breitkreutz, Raoul Herfarth, Christian Meuer, Stefan C. J Exp Med Brief Definitive Report Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low proliferative potential both in vivo and in vitro. Here, we have identified that the capacity of antigen-presenting cells to release cysteine upon receptor–ligand interactions represents a critical parameter for proliferation of LP-Ts. The availability of cysteine is limiting for the intracellular production of glutathione, which in turn is essential for cell cycle progression. When cysteine is provided either directly or by addition of the reducing agent 2-mercaptoethanol to cystine-containing culture medium, proliferation of LP-T is fully restored. Importantly, coculture with peripheral blood monocytes that easily take up cystine, reduce cystine, and secrete cysteine also restores reactivity of LP-Ts to T cell receptor/CD3 stimulation. In marked contrast, lamina propria macrophages lack this capacity to elaborate cysteine, and thereby secure physiological unresponsiveness to antigen exposure in the intestinal microenvironment. The well-documented local recruitment of blood monocytes in inflammatory bowel disease (IBD) may thus represent an important parameter underlying hyperresponsiveness of T cells, an essential component of the pathogenesis of IBD. The Rockefeller University Press 2000-09-18 /pmc/articles/PMC2193281/ /pubmed/10993921 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Sido, Bernd
Braunstein, Jutta
Breitkreutz, Raoul
Herfarth, Christian
Meuer, Stefan C.
Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes
title Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes
title_full Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes
title_fullStr Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes
title_full_unstemmed Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes
title_short Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes
title_sort thiol-mediated redox regulation of intestinal lamina propria t lymphocytes
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193281/
https://www.ncbi.nlm.nih.gov/pubmed/10993921
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