Involvement of CCL25 (TECK) in the generation of the murine small-intestinal CD8alpha alpha+CD3+ intraepithelial lymphocyte compartment

Eur J Immunol. 2002 Dec;32(12):3488-97. doi: 10.1002/1521-4141(200212)32:12<3488::AID-IMMU3488>3.0.CO;2-E.


The CC chemokine CCL25 (TECK) is selectively expressed in the thymus and small intestine, indicating a potential role in T lymphocyte development. In the present study we examined the role of CCL25 in the generation of the small-intestinal CD8alpha alpha(+)CD3(+) intraepithelial lymphocyte (IEL) compartment. CCL25 mRNA expression in the murine small intestine increased at three weeks of age and corresponded with the appearance of CD8alpha alpha(+)CD3(+) lymphocytes in the small-intestinal epithelium. Administration of monoclonal neutralizing anti-CCL25 antibody to two-week-old mice led to a approximately 50% reduction in the total number of CD8alpha alpha(+)TCRgamma delta(+) and CD8alpha alpha(+)TCRalpha beta(+) IEL at four weeks of age. Freshly isolated murine CD8alpha alpha(+)CD3(+) IEL migrated in response to CCL25 and expressed the CCL25 receptor, CCR9. Analysis of CCR9 expression on putative IEL precursor populations demonstrated the presence of both CCR9(-) and CCR9(+) cells and indicated that up-regulation of this receptor occurred during IEL precursor differentiation. Finally, data from wild-type and RAG(-/-) mice suggested that the reduction in CD8alpha alpha(+)CD3(+) IEL in anti-CCL25 antibody treated mice resulted primarily from defective maintenance and/or development of IEL precursors rather than a direct effect on mature CD8alpha alpha(+)CD3(+) IEL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Survival
  • Chemokines, CC / antagonists & inhibitors
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism*
  • Chemotaxis, Leukocyte
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Genes, RAG-1
  • Intestine, Small / cytology*
  • Intestine, Small / immunology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*


  • CD3 Complex
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Ccl25 protein, mouse
  • Chemokines, CC
  • RNA, Messenger