Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells

被引:301
作者
Fehniger, TA
Suzuki, K
Ponnappan, A
VanDeusen, JB
Cooper, MA
Florea, SM
Freud, AG
Robinson, ML
Durbin, J
Caligiuri, MA
机构
[1] Ohio State Univ, Dept Internal Med, Div Hematol Oncol, Columbus, OH 43210 USA
[2] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Div Human Canc Genet, Columbus, OH 43210 USA
[3] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
[4] Gunma Univ, Sch Med, Dept Urol, Gunma 3718511, Japan
[5] Childrens Hosp, Columbus, OH 43205 USA
[6] Res Inst, Columbus, OH 43205 USA
关键词
interleukin; 15; leukemia; transgenic mice; lymphocytes; inflammation;
D O I
10.1084/jem.193.2.219
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Inflammation likely has a role in the early genesis of certain malignancies. Interleukin (IL)-15, a proinflammatory cytokine and growth factor, is required for lymphocyte homeostasis. Intriguingly, the expression of IL-15 protein is tightly controlled by multiple posttranscriptional mechanisms. Here, we engineered a transgenic mouse to overexpress IL-15 by eliminating these posttranscriptional checkpoints. IL-15 transgenic mice have early expansions in natural killer (NK) and CD8(+) T lymphocytes. Later, these mice develop fatal lymphocytic leukemia with a T-NK phenotype. These data provide novel evidence that leukemia, like certain other cancers, can arise as the result of chronic stimulation by a proinflammatory cytokine.
引用
收藏
页码:219 / 231
页数:13
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