C-Myc regulation by costimulatory signals modulates the generation of CD8 + memory T cells during viral infection
| Autor: | Jianyong Song, Xinmeng Song, Youfei Wang, Mohammad Nazmul Haque, Deyu Fang, Jianxun Song, Christopher C. Norbury, Praneet Sandhu, Bing Ni, Shahram Salek-Ardakani, Kristin Fino |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
cd8+ t cells Transcription Genetic Survivin Immunology bcl-X Protein Mice Transgenic CD8-Positive T-Lymphocytes Biology Inhibitor of apoptosis General Biochemistry Genetics and Molecular Biology Inhibitor of Apoptosis Proteins Proto-Oncogene Proteins c-myc memory 03 medical and health sciences Interleukin 21 CD28 Antigens c-myc Animals Cytotoxic T cell IL-2 receptor lcsh:QH301-705.5 Research Articles Research General Neuroscience Immunity NF-kappa B CD28 Receptors OX40 NFKB1 I-kappa B Kinase 3. Good health Cell biology Repressor Proteins 030104 developmental biology Gene Expression Regulation costimulation lcsh:Biology (General) Virus Diseases viral infection Immunologic Memory CD8 Signal Transduction |
| Zdroj: | Open Biology, Vol 6, Iss 1 (2016) Open Biology |
| ISSN: | 2046-2441 |
| Popis: | The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8 + T cells is controlled by costimulatory molecules, which modulates the development of memory CD8 + T cells. C-Myc expression was dramatically reduced in Cd28 −/− or Ox40 −/− memory CD8 + T cells, and c-Myc over-expression substantially reversed the defects in the development of T-cell memory following viral infection. C-Myc regulated the expression of survivin, an inhibitor of apoptosis, which promoted the generation of virus-specific memory CD8 + T cells. Moreover, over-expression of survivin with bcl-xL, a downstream molecule of NF- κ B and intracellular target of costimulation that controls survival, in Cd28 −/− or Ox40 −/− CD8 + T cells, reversed the defects in the generation of memory T cells in response to viral infection. These results identify c-Myc as a key controller of memory CD8 + T cells from costimulatory signals. |
| Databáze: | OpenAIRE |
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