title: Random migration contributes to cytotoxicity of activated CD8+ T-lymphocytes but not NK cells.
abstract: 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.
authors: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ohnishi@surg1.med.kyushu-u.ac.jp.
authors: Hideya
authors: H
authors: Onishi
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Akifumi
authors: A
authors: Kiyota
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Norihiro
authors: N
authors: Koya
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Hiroto
authors: H
authors: Tanaka
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Masayo
authors: M
authors: Umebayashi
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Mitsuo
authors: M
authors: Katano
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Takashi
authors: T
authors: Morisaki
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C
keywords: CD8+ T cell; NK cell; Random migration; cytotoxicity; immunotherapy