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Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8278-83. doi: 10.1073/pnas.1602899113. Epub 2016 Jul 6.

CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7- and IL-15-dependent niches.

Author information

1
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.
2
Department of Pharmacy, Korea University, Sejong City 30019, Korea;
3
Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510;
4
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.

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.

KEYWORDS:

CCR7; IL-15; IL-7; homeostasis; memory T cell

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