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 γδ+ gut intraepithelial lymphocytes

• Published in: Blood Vol. 98; no. 9; pp. 2626 - 2632
• Main Authors: Wurbel, Marc-André, Malissen, Marie, Guy-Grand, Delphine, Meffre, Eric, Nussenzweig, Michel C., Richelme, Mireille, Carrier, Alice, Malissen, Bernard
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.11.2001; The Americain Society of Hematology
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Experimental and animal immunopathology. Animal models; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunopathology; Lymphokines, interleukins ( function, expression); Medical sciences; Regulatory factors and their cellular receptors; Animal model; Lymphopoiesis; Thymus gland; CCR9 chemokine receptor; γ/δ T cell receptor; Thymocyte; Deficiency; Mucosa; Rodentia; Gut; B-Lymphocyte; Chemokine receptor; CC chemokine; Cell differentiation; Chemotaxis; Vertebrata; Local immunity; Mammalia; Mouse; Animal; T-Lymphocyte; Homing phenomenon
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.9.2626

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 double- and single-positive 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 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 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 CCR9−/−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 γδ+ compartment.