Impaired accumulation of antigen-specific CD8 lymphocytes in chemokine CCL25-deficient intestinal epithelium and lamina propria.
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.
Wurbel
Marc-André
MA
Department of Dermatology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA.
Malissen
Marie
M
Guy-Grand
Delphine
D
Malissen
Bernard
B
Campbell
James J
JJ
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D007114:Immunization; D007156:Immunologic Memory; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology; D013950:Thymus Gland / Q000276:immunology
C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D011948:Receptors, Antigen, T-Cell; D054388:Receptors, CCR; D019707:Receptors, Chemokine