Differential effects of interleukin-12 and interleukin-15 on expansion of NK cell receptor-expressing CD8+ T cells.
The cytolytic activity of cells expressing natural killer cell receptors (NKRs) depends on the balance between stimulatory and inhibitory signals. We investigated both inhibitory NK receptor (CD94/NKG2A) expression and stimulatory NKR (NKG2D) expression on T cells after stimulation with cytokines (IL-12 or IL-15). Cytolytic NKR-expressing CD8(+) T cells were expanded from normal adult peripheral blood mononuclear cells using anti-CD3 monoclonal antibody and cytokines (IL-12 or IL-15). The proportion and absolute number of CD94/NKG2A-expressing T cells expanded by IL-12 were significantly larger than those of the cells expanded by IL-15. On the other hand, the proportion and absolute number of NKG2D-expressing T cells expanded by IL-15 were significantly larger than those of the cells expanded by IL-12. The proportions of NKG2D and intracellular granzyme A expression in CD94-expressing cells were much more increased in PBMCs cultured with IL-15 than those of cells cultured with IL-12. A real-time polymerase chain reaction assay showed that there was a 1.68-fold increase in NKG2D mRNA expression level and a 1.37-fold increase in DAP10 mRNA expression level in CD94-expressing cells expanded by IL-15 compared with those of the cells expanded by IL-12. The cytolytic activity levels of purified CD94-expressing cells from 8-day culture with IL-15 tested against (51)Cr-labeled K562 cells by standard 4-h (51)Cr release assays without prior sensitization were much higher than those of cells from 8-day culture with IL-12. IL-15 appears to be able to enhance the cytolytic activity of CD94/NKG2A-expressing cells through induction of NKG2D and intracellular granzyme expression much more efficiently than does IL-12.
Sugita
Junichi
J
Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan. junichi_s@pop21.odn.ne.jp
Tanaka
Junji
J
Yasumoto
Atsushi
A
Shiratori
Souichi
S
Wakasa
Kentaro
K
Kikuchi
Misato
M
Shigematsu
Akio
A
Kondo
Takeshi
T
Asaka
Masahiro
M
Imamura
Masahiro
M
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology*; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism*; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D016133:Polymerase Chain Reaction
D019409:Interleukin-15; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D018664:Interleukin-12