Random migration contributes to cytotoxicity of activated CD8+ T-lymphocytes but not NK cells

Activated lymphocytes have the ability to undergo non-directional cell movement known as random migration, although the biological role for this remains unclear. Herein, we investigated how random migration affects cytotoxicity of activated lymphocytes using time-lapse imaging analysis. The kinetics...

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Bibliographic Details
Published in:Anticancer research 2014-08, Vol.34 (8), p.3947-3956
Main Authors: Onishi, Hideya, Kiyota, Akifumi, Koya, Norihiro, Tanaka, Hiroto, Umebayashi, Masayo, Katano, Mitsuo, Morisaki, Takashi
Format: Article
Language:English
Subjects:
Animals
CD8-Positive T-Lymphocytes - immunology
Cell Movement
Cytotoxicity, Immunologic
Female
Humans
Immunotherapy
Killer Cells, Natural - immunology
Lymphocyte Activation
Mice
Mice, Inbred BALB C
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Summary:Activated lymphocytes have the ability to undergo non-directional cell movement known as random migration, although the biological role for this remains unclear. Herein, we investigated how random migration affects cytotoxicity of activated lymphocytes using time-lapse imaging analysis. The kinetics of random migration paralleled cytotoxicity in activated lymphocytes. Sphingosine-1-phosphate (S1P) and its receptor-1 (S1PR1) play an important role in lymphocyte migration. Phosphorylated FTY720 (FTYP), a structural analog of S1P, significantly inhibited random migration and cytotoxicity of activated CD3(+)NKG2D(+)CD8(+) T-lymphocytes but not CD3(-)NKG2D(+)CD56(+) natural killer (NK) cells. In a mouse xenograft model, FTYP-treated activated lymphocytes exhibited lower cytotoxicity and less tumor infiltration for activated CD3(+)NKG2D(+) T-lymphocytes but not CD3(-)NKG2D(+) NK cells. These results suggest that random migration contributes to the cytotoxicity of activated CD8(+) T-cells but not of NK cells.
ISSN:1791-7530