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 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.