The immunosuppressive agent FK506 enhances the cytolytic activity of inhibitory natural killer cell receptor (CD94/NKG2A)-expressing CD8 T cells.
Tacrolimus (FK506) is a potent immunosuppressive agent that inhibit transcription of cytokines such as IL-2 in T cells. The C-type lectin superfamily inhibitory NKR CD94/NKG2A-expressing cells can monitor the global status of HLA class I on tumor and leukemic cells through the recognition of HLA-E and induce cytolytic attack without an inhibitory signal against HLA class I-decreased target cells. We found that there was no effect of FK506 on the expansion of inhibitory NKR CD94/NKG2A-expressing T cells from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs). However, cytolytic activity levels of purified CD94-expressing cells from 7-day cultures with FK506 were much higher than those from 7-day cultures without FK506. These data suggested that FK506 did not inhibit cytolytic activities of inhibitory NKR-expressing T cells and that there was a possibility of cytolytic activities being enhanced through the induction of cytotoxic molecules such as NKG2D and granzyme during a seven-day culture with FK506.
Tanaka
Junji
J
Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. jutanaka@med.hokudai.ac.jp
Toubai
Tomomi
T
Iwao
Noriaki
N
Tsutsumi
Yutaka
Y
Kato
Naoko
N
Miura
Yoko
Y
Shigematsu
Akio
A
Hirate
Daisuke
D
Ota
Shuichi
S
Asaka
Masahiro
M
Imamura
Masahiro
M
D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D019409:Interleukin-15; C497869:KLRD1 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016559:Tacrolimus