CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice
CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice
Transfer of CD45RBhigh CD4+ T cells to immune-deficient mice in the absence of regulatory T cells leads to a Th1-mediated colitis. In this study, we show that intestinal inflammation is characterized by a 15-fold increase in the number of CD134L+ (OX40L+)-activated DC in the mesenteric lymph nodes (MLNs) compared with BALB/c mice. This was important functionally, as administration of an anti-CD134L mAb inhibited the proliferation of T cells in the MLNs as well as their expression of the gut-homing integrin ?4?7. Most importantly, the anti-CD134L mAb completely blocked development of colitis. Surprisingly, CD134L was found to be expressed by a proportion of dendritic cells (DC) in the MLNs of unreconstituted SCID mice, suggesting that CD134L can be induced on DC in the absence of T cell-derived signals. These results indicate that some DC in the MLNs of SCID mice express an activated phenotype and that CD134L expression by these cells is involved in the development of colitis induced by T cell transfer. Accumulation of CD134L+ DC was inhibited by cotransfer of regulatory T cells, suggesting that inhibition of the accumulation of activated DC is one mechanism by which these cells prevent immune pathology.
6972-6981
Malmström, Vivianne
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Shipton, Deborah
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Singh, Baljit
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Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Puklavec, Michael J.
128cff6c-81fd-4258-a940-6c25f725ff55
Barclay, A. Neil
5199192a-78a1-4a00-946c-bced641ee10a
Powrie, Fiona
82f0da2d-4286-4a82-8e5c-965284fdc848
2001
Malmström, Vivianne
2f29bb3d-6136-4da9-8196-b580953f4bed
Shipton, Deborah
b6fffdc6-d2d3-421a-8052-941874c01f43
Singh, Baljit
c267e7fc-f51b-45ed-b7b4-e2498a60620d
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Puklavec, Michael J.
128cff6c-81fd-4258-a940-6c25f725ff55
Barclay, A. Neil
5199192a-78a1-4a00-946c-bced641ee10a
Powrie, Fiona
82f0da2d-4286-4a82-8e5c-965284fdc848
Malmström, Vivianne, Shipton, Deborah, Singh, Baljit, Al-Shamkhani, Aymen, Puklavec, Michael J., Barclay, A. Neil and Powrie, Fiona
(2001)
CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice.
Journal of Immunology, 166 (11), .
Abstract
Transfer of CD45RBhigh CD4+ T cells to immune-deficient mice in the absence of regulatory T cells leads to a Th1-mediated colitis. In this study, we show that intestinal inflammation is characterized by a 15-fold increase in the number of CD134L+ (OX40L+)-activated DC in the mesenteric lymph nodes (MLNs) compared with BALB/c mice. This was important functionally, as administration of an anti-CD134L mAb inhibited the proliferation of T cells in the MLNs as well as their expression of the gut-homing integrin ?4?7. Most importantly, the anti-CD134L mAb completely blocked development of colitis. Surprisingly, CD134L was found to be expressed by a proportion of dendritic cells (DC) in the MLNs of unreconstituted SCID mice, suggesting that CD134L can be induced on DC in the absence of T cell-derived signals. These results indicate that some DC in the MLNs of SCID mice express an activated phenotype and that CD134L expression by these cells is involved in the development of colitis induced by T cell transfer. Accumulation of CD134L+ DC was inhibited by cotransfer of regulatory T cells, suggesting that inhibition of the accumulation of activated DC is one mechanism by which these cells prevent immune pathology.
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Published date: 2001
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Local EPrints ID: 26459
URI: http://eprints.soton.ac.uk/id/eprint/26459
ISSN: 0022-1767
PURE UUID: a8290197-4aa3-4855-ac6b-84c15e29a5ec
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Date deposited: 21 Apr 2006
Last modified: 23 Jul 2022 01:44
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Contributors
Author:
Vivianne Malmström
Author:
Deborah Shipton
Author:
Baljit Singh
Author:
Michael J. Puklavec
Author:
A. Neil Barclay
Author:
Fiona Powrie
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