title: The immunosuppressive agent FK506 enhances the cytolytic activity of inhibitory natural killer cell receptor (CD94/NKG2A)-expressing CD8 T cells.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. jutanaka@med.hokudai.ac.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Toubai
authors.forename: Noriaki
authors.initials: N
authors.lastname: Iwao
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Naoko
authors.initials: N
authors.lastname: Kato
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miura
authors.forename: Akio
authors.initials: A
authors.lastname: Shigematsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hirate
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ota
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
mesh_terms: 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*
chemical_list: D007166:Immunosuppressive Agents; D019409:Interleukin-15; C497869:KLRD1 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016559:Tacrolimus