Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

• Published in: Journal of Immunology 2007-06, Vol.178 (12), p.7598-7606
• Main Authors: Wurbel, Marc-Andre, Malissen, Marie, Guy-Grand, Delphine, Malissen, Bernard, Campbell, James J
• Format: Article
• Language: English
• Subjects: Adaptive immunology; Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes - immunology; Cell Movement - genetics; Cell Movement - immunology; Chemokines, CC - genetics; Chemokines, CC - physiology; Immunization; Immunologic Memory; Immunology; Intestinal Mucosa - immunology; Intestines - immunology; Life Sciences; Mice; Mice, Mutant Strains; Mice, Transgenic; Mucous Membrane - immunology; Phenotype; Receptors, Antigen, T-Cell - genetics; Receptors, CCR; Receptors, Chemokine - genetics; Receptors, Chemokine - physiology; Thymus Gland - immunology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.178.12.7598

CCL25 and CCR9 constitute a chemokine/receptor pair involved in T cell development and in gut-associated immune responses. In this study, we generated CCL25(-/-) mice to answer questions that could not be addressed with existing CCR9(-/-) mice. Similar phenotypes were observed for both CCL25(-/-) and CCR9(-/-) mice, consistent with the notion that CCL25 and CCR9 interact with each other exclusively. We assessed the requirement for CCL25 in generating CCR9(high) CD8 intestinal memory-phenotype T cells and the subsequent accumulation of these cells within effector sites. TCR-transgenic naive CD8 T cells were transferred into wild-type or CCL25-deficient hosts. Oral sensitization with Ag allowed these naive donor cells to efficiently differentiate into CCR9(high) memory-phenotype cells within the mesenteric lymph nodes of wild-type hosts. This differentiation event occurred with equal efficiency in the MLN of CCL25-deficient hosts, demonstrating that CCL25 is not required to induce the CCR9(high) memory phenotype in vivo. However, we found that CCL25 deficiency severely impaired the Ag-dependent accumulation of donor-derived CD8 T cells within both lamina propria and epithelium of the small intestine. Thus, although CCL25 is not necessary for generating memory-phenotype CD8 T cells with "gut-homing" properties, this chemokine is indispensable for their trafficking to the small intestine.