Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma

Journal of Translational Medicine

Bo Zhu²  Zhongquan Zhao²  Tong Xiang²  Wei Qi²  Luhang He²  Haixia Long²  Xiaoming Cheng¹  Guocheng Zhong² 

[1] Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People’s Republic of China;Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People’s Republic of China

关键词: Memory T cell;    Immune function;    CD8+ T lymphocyte;    microRNA-15b;   

Others  :  827910
DOI  :  10.1186/1479-5876-11-71

 received in 2012-12-03, accepted in 2013-03-13,  发布年份 2013

【 摘 要 】

Background

CD8+ T cells are key members of adaptive immunity against tumorigenesis. As subset of CD8+ T cells, effector T cells (Te) and memory T cells (Tm) have different biological activities. The former can kill tumor cells but come into apoptosis in a certain period and the latter is static with the ability of self-renewal. Previous studies showed that microRNAs (miRNA) played critical roles in regulating adaptive immunity. This study aimed to identify the different expression of miRNAs between Te and Tm cells in tumor-bearing mice and to sort out the target miRNAs which can be regulated to improve anti-tumor activities of CD8+ T cells.

Methods

miRNA expression profiling was performed on CD8+ Te and Tm cells from mice with Lewis lung carcinoma. Differentially expressed miRNA (miRNA-15b) was chosen and analyzed by qRT-PCR. Then, flow cytometry, ELISA, and CFSE kit were used to evaluate the biological effects of miRNA-15b on apoptosis, cytokine secretion, phenotype, and proliferation of CD8+ T cell. The possible downstream target genes of this miRNA were also analyzed.

Results

Analysis of miRNA microarray and qRT-PCR showed that the level of miRNA-15b was higher in CD8+ Tm cells than in Te cells. Higher expression of miRNA-15b was observed in CD8+ T cells from tumor-bearing mice than those from healthy ones. Transfection of CD8+ T cells with miRNA-15b mimics could prevent T cells from apoptosis by inhibiting the translation of DEDD (Death Effector Domain-containing DNA binding protein). Moreover, ectopic miRNA-15b could inhibit the activation of CD8+ T cells (via repressing the production of IL-2 and IFN-γ and expression of CD69) and promote expression of CD44 through unknown pathways.

Conclusion

Up-regulation of miRNA-15b in tumor environment might negatively regulate anti-tumor immunity through inhibiting function of CD8+ T cells. miRNA-15b might be a potential therapeutic target for immunotherapy.

【 授权许可】

   
2013 Zhong et al.; licensee BioMed Central Ltd.

【 图 表 】

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