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| Item Type: | Article |
|---|---|
| Title: | Luminal CD4 + T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation |
| Creators Name: | Nemoto, Y., Kanai, T., Shinohara, T., Ito, T., Nakamura, T., Okamoto, R., Tsuchiya, K., Lipp, M., Eishi, Y. and Watanabe, M. |
| 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 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 {alpha}-deficient mice were crossed with RAG-2-/-mice to generate LT{alpha}-/-x 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 h, but were not found in spleen until 24 h after administration. Immunohistochemical and electron microscopic analyses detected CD4+ T cells in the intraepithelial space just 3 h after intrarectal administration. However, neither CCR7 deficiency nor the sphingosine-1-phosphate receptor agonist FTY720 impaired the egress of CD4+ T cells from LP to systemic circulation. CONCLUSION: 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. |
| Keywords: | T-Cell Migration, Localization, Mouse Model, Chemokine, Treatment, Animals, Mice |
| Source: | Gastroenterology |
| ISSN: | 0016-5085 |
| Publisher: | Elsevier / Saunders |
| Volume: | 141 |
| Number: | 6 |
| Page Range: | 2130-2139.e11 |
| Date: | December 2011 |
| Official Publication: | https://doi.org/10.1053/j.gastro.2011.08.035 |
| PubMed: | View item in PubMed |
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