Cutting Edge: Cure of Colitis by CD4+CD25+ Regulatory T Cells

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CUTTING EDGE

Cutting Edge: Cure of Colitis by CD4⁺CD25⁺ Regulatory T Cells¹

Christian Mottet², Holm H. Uhlig² and Fiona Powrie³

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

CD4⁺CD25⁺ regulatory T cells have been shown to prevent T cell-mediatedimmune pathology; however, their ability to ameliorate establishedinflammation has not been tested. Using the CD4⁺CD45RB^high Tcell transfer model of inflammatory bowel disease, we show thatCD4⁺CD25⁺ but not CD4⁺CD25^-CD45RB^low T cells are able to cureintestinal inflammation. Transfer of CD4⁺CD25⁺ T cells intomice with colitis led to resolution of the lamina propria infiltratein the intestine and reappearance of normal intestinal architecture.CD4⁺CD25⁺ T cells were found to proliferate in the mesentericlymph nodes and inflamed colon. They were located between clustersof CD11c⁺ cells and pathogenic T cells and found to be in contactwith both cell types. These studies suggest that manipulationof CD4⁺CD25⁺ T cells may be beneficial in the treatment of chronicinflammatory diseases.

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Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets
PNAS, February 8, 2005; 102(6): 2010 - 2015.
[Abstract] [Full Text] [PDF]

C Veltkamp, R B Sartor, T Giese, F Autschbach, I Kaden, R Veltkamp, D Rost, B Kallinowski, and W Stremmel
Regulatory CD4+CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TG{varepsilon}26 mice leading to the prevention of colitis
Gut, February 1, 2005; 54(2): 207 - 214.
[Abstract] [Full Text] [PDF]

A Radbruch and A Thiel
Cell therapy for autoimmune diseases: does it have a future?
Ann Rheum Dis, November 1, 2004; 63(suppl_2): ii96 - ii101.
[Abstract] [Full Text] [PDF]

S. Makita, T. Kanai, S. Oshima, K. Uraushihara, T. Totsuka, T. Sawada, T. Nakamura, K. Koganei, T. Fukushima, and M. Watanabe
CD4+CD25bright T Cells in Human Intestinal Lamina Propria as Regulatory Cells
J. Immunol., September 1, 2004; 173(5): 3119 - 3130.
[Abstract] [Full Text] [PDF]

C. Baecher-Allan and D. A. Hafler
Suppressor T Cells in Human Diseases
J. Exp. Med., August 2, 2004; 200(3): 273 - 276.
[Abstract] [Full Text] [PDF]

D S Robinson
Regulation: the art of control? Regulatory T cells and asthma and allergy
Thorax, August 1, 2004; 59(8): 640 - 643.
[Full Text] [PDF]

E. A. Wohlfert, M. K. Callahan, and R. B. Clark
Resistance to CD4+CD25+ Regulatory T Cells and TGF-{beta} in Cbl-b-/- Mice
J. Immunol., July 15, 2004; 173(2): 1059 - 1065.
[Abstract] [Full Text] [PDF]

S. Paust, L. Lu, N. McCarty, and H. Cantor
Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease
PNAS, July 13, 2004; 101(28): 10398 - 10403.
[Abstract] [Full Text] [PDF]

K. V. Tarbell, S. Yamazaki, K. Olson, P. Toy, and R. M. Steinman
CD25+ CD4+ T Cells, Expanded with Dendritic Cells Presenting a Single Autoantigenic Peptide, Suppress Autoimmune Diabetes
J. Exp. Med., June 7, 2004; 199(11): 1467 - 1477.
[Abstract] [Full Text] [PDF]

A. E. Herman, G. J. Freeman, D. Mathis, and C. Benoist
CD4+CD25+ T Regulatory Cells Dependent on ICOS Promote Regulation of Effector Cells in the Prediabetic Lesion
J. Exp. Med., June 7, 2004; 199(11): 1479 - 1489.
[Abstract] [Full Text] [PDF]

N. A. Danke, D. M. Koelle, C. Yee, S. Beheray, and W. W. Kwok
Autoreactive T Cells in Healthy Individuals
J. Immunol., May 15, 2004; 172(10): 5967 - 5972.
[Abstract] [Full Text] [PDF]

S. Suvas, A. K. Azkur, B. S. Kim, U. Kumaraguru, and B. T. Rouse
CD4+CD25+ Regulatory T Cells Control the Severity of Viral Immunoinflammatory Lesions
J. Immunol., April 1, 2004; 172(7): 4123 - 4132.
[Abstract] [Full Text] [PDF]