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 gd1 gut intraepithelial lymphocytes

CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/ thymus-expressed chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was deleted. In spite of the high level of CCR9 found in doubleand singlepositive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrathymic T-cell development. It was noted that there was only a one-day lag in the appearance of doublepositive cells during fetal ontogeny in CCR92/2 thymi. When tested in chemotaxis assay, thymocytes isolated from CCR92/2 mice failed to respond to TECK/ CCL25. Taken together, these results suggest 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 pre-pro–B cells in CCR92/2 mice than in wild-type mice. However, this diminution does not appear to have a detectable effect on the generation of a normal 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 marked diminution of the T-cell receptor gd1 compartment. (Blood. 2001;98:2626-2632)