Differential effects of interleukin-12 and interleukin-15 on expansion of NK cell receptor-expressing CD8⁺ T cells

• Published in: Annals of hematology Vol. 89; no. 2; pp. 115 - 120
• Main Authors: Sugita, Junichi, Tanaka, Junji, Yasumoto, Atsushi, Shiratori, Souichi, Wakasa, Kentaro, Kikuchi, Misato, Shigematsu, Akio, Kondo, Takeshi, Asaka, Masahiro, Imamura, Masahiro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.02.2010; Springer-Verlag; Springer Nature B.V
• Subjects: Adult; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - drug effects; Cell Line; Cell Survival - drug effects; Cells, Cultured; Flow Cytometry; Hematology; Humans; Interleukin-12 - pharmacology; Interleukin-15 - pharmacology; Medicine; Medicine & Public Health; NK Cell Lectin-Like Receptor Subfamily C - metabolism; NK Cell Lectin-Like Receptor Subfamily D - metabolism; NK Cell Lectin-Like Receptor Subfamily K - metabolism; Oncology; Original Article; Polymerase Chain Reaction; Cytolytic activity; NKG2D; CD94; NKG2A
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-009-0780-0

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 ⁵¹Cr-labeled K562 cells by standard 4-h ⁵¹Cr 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.