Yong Woo Junga,b,1, Hyun Gyung Kimb, Curtis J. Perrya, and Susan M. Kaecha,c,1
aDepartment of Immunobiology, Yale School of Medicine, New Haven, CT 06510;
bDepartment of Pharmacy, Korea University, Sejong City 30019, Korea;
cHoward Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06510
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.
CCR7, memory T cell, IL-7, IL-15, homeostasis
1To whom correspondence may be addressed.
Author contributions: Y.W.J. and S.M.K. designed research; Y.W.J. and H.G.K. performed research; H.G.K. and C.J.P. contributed new reagents/analytic tools; Y.W.J., H.G.K., C.J.P., and S.M.K. analyzed data; and Y.W.J. and S.M.K. wrote the paper.