Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gamma delta(+) gut intraepithelial lymphocytes

CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/thym us-expressed chemokine (TECK), is mainly expressed by thymocytes and by int raepithelial (IEL) and lamina propria lymphocytes of the small Intestine. T o study the biologic role of CCR9, a mouse strain was generated in which th e CCR9 gene was deleted. In spite of the high level of CCR9 found in double -and single-positive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrat hymic T-cell develop ment. It was noted that there was only a one-day lag I n the appearance of double-positive cells during fetal ontogeny in CCR9(-/- ) thymi. When tested in chemotaxis assay, thymocytes isolated from CCR9(-/- ) mice failed to respond to TECK/CCL25. Taken together, these results sugge st that In thymocytes, CCR9 is the only physiologic receptor for TECK/CCL25 , and that it is dispensable for proper T-cell development. Bone marrow pre -pro-B cells migrate in response to TECK/CCL25, but more mature B cells do not. Consistent with this observation, it was shown that there are fewer pr e-pro-B cells in CCR9(-/-) mice than in wild-type mice. However, this dimin ution does not appear to have a detectable effect on the generation of a no rmal complement of mature B cells. Finally, it was shown that in the small intestine of CCR9-deficient mice, the intraepithelial T-cell-to-epithelial cell ratio Is decreased, an observation that can be accounted for by a mark ed diminution of the T-cell receptor gamma delta (+) compartment. (C) 2001 by The American Society of Hematology.