title: CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7- and IL-15-dependent niches.
abstract: C-C receptor 7 (CCR7) is important to allow T cells and dendritic cells to migrate toward CCL19- and CCL21-producing cells in the T-cell zone of the spleen and lymph nodes. The role of this chemokine receptor in regulating the homeostasis of effector and memory T cells during acute viral infection is poorly defined, however. In this study, we show that CCR7 expression alters memory CD8 T-cell homeostasis following lymphocytic choriomeningitis virus infection. Greater numbers of CCR7-deficient memory T cells were formed and maintained compared with CCR7-sufficient memory T cells, especially in the lung and bone marrow. The CCR7-deficient memory T cells also displayed enhanced rates of homeostatic turnover, which may stem from increased exposure to IL-15 as a consequence of reduced exposure to IL-7, because removal of IL-15, but not of IL-7, normalized the numbers of CCR7-sufficient and CCR7-deficient memory CD8 T cells. This result suggests that IL-15 is the predominant cytokine supporting augmentation of the CCR7(-/-) memory CD8 T-cell pool. Taken together, these data suggest that CCR7 biases memory CD8 T cells toward IL-7-dependent niches over IL-15-dependent niches, which provides insight into the homeostatic regulation of different memory T-cell subsets.
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510; Department of Pharmacy, Korea University, Sejong City 30019, Korea; yjung@korea.ac.kr susan.kaech@yale.edu.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Jung
authors.affiliation: Department of Pharmacy, Korea University, Sejong City 30019, Korea;
authors.forename: Hyun Gyung
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510;
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Perry
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510; Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06510 yjung@korea.ac.kr susan.kaech@yale.edu.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006706:Homeostasis; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology; D008216:Lymphocytic Choriomeningitis / Q000097:blood / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology
chemical_list: C515371:Ccr7 protein, mouse; D019409:Interleukin-15; D015851:Interleukin-7; D054400:Receptors, CCR7
keywords: CCR7; IL-15; IL-7; homeostasis; memory T cell