Abstract | BACKGROUND & AIMS: The egress of memory T cells from peripheral tissues, such as lung and skin, into the draining lymph nodes requires their expression of CC chemokine receptor 7 (CCR7). In the intestine, resident memory T cells in the intestinal lamina propria (LP) do not express CCR7, indicating that they are tissue bound and do not exit the intestine. METHODS: We developed a cell transfer system, using rectal administration of lymphocytes to C57BL/6 mice. Lymphotoxin α-deficient mice were crossed with RAG-2(-/-) (recombination-activating gene-2) mice to generate lymphotoxin α-deficient × RAG-2(-/-) mice. RESULTS: Severe combined immunodeficient (SCID) or RAG-2(-/-) mice given rectal administration of splenic CD4(+) T cells from normal mice developed colitis; the cells proliferated not only in the LP but also in spleen. SCID or RAG-2(-/-) mice given rectal administrations of CD4(+) T cells that expressed green fluorescent protein (GFP(+)CD4(+) T cells) localized to the LP within 6 hours but were not found in the spleen until 24 hours after administration. Immunohistochemical and electron microscopic analyses detected CD4(+) T cells in the intraepithelial space just 3 hours after intrarectal administration. However, neither CCR7 deficiency nor the sphingosine-1-phosphate receptor agonist Fingolimod impaired the egress of CD4(+) T cells from LP to systemic circulation. CONCLUSIONS: CD4(+) T cells not only penetrate from the luminal side of the intestine to the LP but also actively egress from the LP into the circulation. We developed a rectal administration system that might be used to further investigate cell trafficking in intestinal mucosa and to develop enema-based therapeutics for intestinal diseases.
|
Authors | Yasuhiro Nemoto, Takanori Kanai, Tamako Shinohara, Takashi Ito, Tetsuya Nakamura, Ryuichi Okamoto, Kiichiro Tsuchiya, Martin Lipp, Yoshinobu Eishi, Mamoru Watanabe |
Journal | Gastroenterology
(Gastroenterology)
Vol. 141
Issue 6
Pg. 2130-2139.e11
(Dec 2011)
ISSN: 1528-0012 [Electronic] United States |
PMID | 21875496
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
|
Topics |
- Animals
- Blood Circulation
- CD4-Positive T-Lymphocytes
(physiology)
- Cell Movement
(physiology)
- Colitis, Ulcerative
(blood, immunology)
- Humans
- Immunohistochemistry
- Intestinal Mucosa
(immunology)
- Mice
- Mice, Inbred C57BL
- Mice, SCID
- Microscopy, Electron
- Mucous Membrane
(immunology)
- Receptors, CCR7
(metabolism)
|