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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18 September 2000
Brief Definitive Report|
September 18 2000
Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes
Bernd Sido,
Bernd Sido
aDepartment of Surgery, University of Heidelberg, 69120 Heidelberg, Germany
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Jutta Braunstein,
Jutta Braunstein
bInstitute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany
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Raoul Breitkreutz,
Raoul Breitkreutz
cGerman Cancer Research Center, 69120 Heidelberg, Germany
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Christian Herfarth,
Christian Herfarth
aDepartment of Surgery, University of Heidelberg, 69120 Heidelberg, Germany
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Stefan C. Meuer
Stefan C. Meuer
bInstitute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany
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Bernd Sido
aDepartment of Surgery, University of Heidelberg, 69120 Heidelberg, Germany
Jutta Braunstein
bInstitute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany
Raoul Breitkreutz
cGerman Cancer Research Center, 69120 Heidelberg, Germany
Christian Herfarth
aDepartment of Surgery, University of Heidelberg, 69120 Heidelberg, Germany
Stefan C. Meuer
bInstitute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany
Received:
November 12 1999
Revision Requested:
May 19 2000
Accepted:
June 01 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (6): 907–912.
Article history
Received:
November 12 1999
Revision Requested:
May 19 2000
Accepted:
June 01 2000
Citation
Bernd Sido, Jutta Braunstein, Raoul Breitkreutz, Christian Herfarth, Stefan C. Meuer; Thiol-Mediated Redox Regulation of Intestinal Lamina Propria T Lymphocytes. J Exp Med 18 September 2000; 192 (6): 907–912. doi: https://doi.org/10.1084/jem.192.6.907
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