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.
|出版ステータス||出版済み - 8月 1 2014|
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