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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells
  • CD8-Positive T-Lymphocytes / immunology*
  • Homeostasis
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology*
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology*
  • Liver / cytology
  • Lung / cytology
  • Lymph Nodes / cytology
  • Lymphocytic Choriomeningitis / blood
  • Lymphocytic Choriomeningitis / immunology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / immunology*
  • Spleen / cytology


  • Ccr7 protein, mouse
  • Interleukin-15
  • Interleukin-7
  • Receptors, CCR7