Osteopontin modulates the generation of memory CD8+ T cells during influenza virus infection.
The adaptive immune system generates memory cells, which induce a rapid and robust immune response following secondary Ag encounter. Memory CD8(+) T cells are a critical component of protective immunity against infections and cancers. Therefore, understanding the mechanism whereby memory CD8(+) T cells are generated and maintained is important for inducing effective memory CD8(+) T cell response. Recent studies have demonstrated that the inflammatory cytokine IL-12 favors the generation of terminal effector CD8(+) T cells rather than memory precursor effector CD8(+) T cells by regulating the expression of the transcription factor T-bet. In this study, we report that the inflammatory cytokine osteopontin (Opn) modulates memory CD8(+) T cell generation during influenza virus infection. Although Opn wild-type and Opn knockout (KO) mice had similar numbers of virus-specific effector CD8(+) T cells, virus-specific effector CD8(+) T cells generated in Opn KO mice showed low levels of T-bet expression and an increased memory precursor cell population compared with cells generated in Opn wild-type mice. This resulted in the persistently increased number of memory CD8(+) T cells in Opn KO mice. Studies with bone marrow-derived dendritic cells demonstrated that Opn deficiency in bone marrow-derived dendritic cells results in low levels of IL-12 production in response to the stimulation with influenza virus. Thus, we hypothesize that Opn modulates the generation of memory precursor effector CD8(+) T cells by regulating cytokine milieu during the acute phase of virus infection. This finding may provide new insight into the role of Opn in adaptive immune response.
Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan. morimoto@igm.hokudai.ac.jp
Junko
J
Morimoto
Kayoko
K
Sato
Yosuke
Y
Nakayama
Chiemi
C
Kimura
Kiichi
K
Kajino
Yutaka
Y
Matsui
Tadaaki
T
Miyazaki
Toshimitsu
T
Uede
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002469:Cell Separation; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D053495:Osteopontin / Q000276:immunology* / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction
D053495:Osteopontin