Involvement of CCL25 (TECK) in the generation of the murine small-intestinal CD8alpha alpha+CD3+ intraepithelial lymphocyte compartment.
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.
Marsal
Jan
J
Immunology Section, Department of Cell and Molecular Biology, Lund University, Lund, Sweden.
Svensson
Marcus
M
Ericsson
Anna
A
Iranpour
Amir H
AH
Carramolino
Laura
L
Márquez
Gabriel
G
Agace
William W
WW
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002470:Cell Survival; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D016654:Genes, RAG-1; D007421:Intestine, Small / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D017252:CD3 Complex; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D012333:RNA, Messenger