Luminal CD4⁺ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation

Gastroenterology. 2011 Dec;141(6):2130-2139.e11. doi: 10.1053/j.gastro.2011.08.035. Epub 2011 Aug 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Circulation
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Movement / physiology*
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / immunology*
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Microscopy, Electron
  • Mucous Membrane / immunology*
  • Receptors, CCR7 / metabolism


  • Receptors, CCR7