| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;
Department of Microbiology and Immunology, Nihon University School of Density at Matsudo, Matsudo, Japan; and
Department of Microbiology and Immunology, Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only does active suppression by regulatory T (TREG) cells play an important role in the normal intestinal homeostasis, but also that its dysregulation of immune response leads to the development of inflammatory bowel disease. In this study, we demonstrate that murine CD4+CD25+ T cells residing in the intestinal lamina propria (LP) constitutively express CTLA-4, glucocorticoid-induced TNFR, and Foxp3 and suppress proliferation of responder CD4+ T cells in vitro. Furthermore, cotransfer of intestinal LP CD4+CD25+ T cells prevents the development of chronic colitis induced by adoptive transfer of CD4+CD45RBhigh T cells into SCID mice. When lymphotoxin (LT)
-deficient intercrossed Rag2 double knockout mice (LT–/– x Rag2–/–), which lack mesenteric lymph nodes and Peyer’s patches, are transferred with CD4+CD45RBhigh T cells, they develop severe wasting disease and chronic colitis despite the delayed kinetics as compared with the control LT+/+ x Rag2–/– mice transferred with CD4+CD45RBhigh T cells. Of note, when a mixture of splenic CD4+CD25+ TREG cells and CD4+CD45RBhigh T cells are transferred into LT–/– x Rag2–/– recipients, CD4+CD25+ TREG cells migrate into the colon and prevent the development of colitis in LT–/– x Rag2–/– recipients as well as in the control LT+/+ x Rag2–/– recipients. These results suggest that the intestinal LP harboring CD4+CD25+ TREG cells contributes to the intestinal immune suppression.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported in part by grants-in-aid for Scientific Research, Scientific Research on Priority Areas, Exploratory Research and Creative Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology; the Japanese Ministry of Health, Labor and Welfare; the Japan Medical Association; Foundation for Advancement of International Science; Terumo Life Science Foundation; Ohyama Health Foundation; Yakult Bio-Science Foundation; and Research Fund of Mitsukoshi Health and Welfare Foundation.
2 Address correspondence and reprint requests to Dr. Takanori Kanai, Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail address: taka.gast{at}tmd.ac.jp
3 Abbreviations used in this paper: TREG, regulatory T; LP, lamina propria; PP, Peyer’s patch; MLN, mesenteric lymph node; ILF, isolated lymphoid follicle; GITR, glucocorticoid-induced TNFR; LT, lymphotoxin.
This article has been cited by other articles:
|
|
 |
|
  D. R. Withers, E. Jaensson, F. Gaspal, F. M. McConnell, B. Eksteen, G. Anderson, W. W. Agace, and P. J. L. Lane The Survival of Memory CD4+ T Cells within the Gut Lamina Propria Requires OX40 and CD30 Signals J. Immunol., October 15, 2009; 183(8): 5079 - 5084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Totsuka, T. Kanai, Y. Nemoto, T. Tomita, R. Okamoto, K. Tsuchiya, T. Nakamura, N. Sakamoto, H. Akiba, K. Okumura, et al. RANK-RANKL Signaling Pathway Is Critically Involved in the Function of CD4+CD25+ Regulatory T Cells in Chronic Colitis J. Immunol., May 15, 2009; 182(10): 6079 - 6087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D H Adams, B Eksteen, and S M Curbishley Immunology of the gut and liver: a love/hate relationship Gut, June 1, 2008; 57(6): 838 - 848. [Full Text] [PDF]
|
|
|
|
|
|
T. Tomita, T. Kanai, T. Fujii, Y. Nemoto, R. Okamoto, K. Tsuchiya, T. Totsuka, N. Sakamoto, S. Akira, and M. Watanabe MyD88-Dependent Pathway in T Cells Directly Modulates the Expansion of Colitogenic CD4+ T Cells in Chronic Colitis J. Immunol., April 15, 2008; 180(8): 5291 - 5299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Cecchinato, E. Tryniszewska, Z. M. Ma, M. Vaccari, A. Boasso, W.-P. Tsai, C. Petrovas, D. Fuchs, J.-M. Heraud, D. Venzon, et al. Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection J. Immunol., April 15, 2008; 180(8): 5439 - 5447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Guo, M. H. Jang, K. Otani, Z. Bai, E. Umemoto, M. Matsumoto, M. Nishiyama, M. Yamasaki, S. Ueha, K. Matsushima, et al. CD4+CD25+ regulatory T cells in the small intestinal lamina propria show an effector/memory phenotype Int. Immunol., March 1, 2008; 20(3): 307 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tomita, T. Kanai, Y. Nemoto, T. Totsuka, R. Okamoto, K. Tsuchiya, N. Sakamoto, and M. Watanabe Systemic, but Not Intestinal, IL-7 Is Essential for the Persistence of Chronic Colitis J. Immunol., January 1, 2008; 180(1): 383 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ito, T. Kanai, T. Totsuka, R. Okamoto, K. Tsuchiya, Y. Nemoto, A. Yoshioka, T. Tomita, T. Nagaishi, N. Sakamoto, et al. Blockade of NKG2D signaling prevents the development of murine CD4+ T cell-mediated colitis Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G199 - G207. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
