Menin Plays a Critical Role in the Regulation of the Antigen-Specific CD8+ T Cell Response upon Listeria Infection
| Autor: | Saho Maruyama, Masakatsu Yamashita, Takuya Fujimoto, Masaki Yasukawa, Junpei Suzuki, Makoto Kanoh, Shogo Nabe, Takeshi Yamada, Akira Matsumoto, Toshiaki Yasuoka, Makoto Kuwahara, Ryo Sakisuka |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities endocrine system Adoptive cell transfer endocrine system diseases Ovalbumin Transgene Immunology Mice Transgenic CD8-Positive T-Lymphocytes Biology Mice Mice Congenic 03 medical and health sciences 0302 clinical medicine Immune system Proto-Oncogene Proteins Animals Immunology and Allergy Cytotoxic T cell Listeriosis MEN1 Cell Differentiation Cell cycle Adoptive Transfer Listeria monocytogenes Molecular biology Mice Inbred C57BL Haematopoiesis 030104 developmental biology Positive Regulatory Domain I-Binding Factor 1 T-Box Domain Proteins CD8 Transcription Factors 030215 immunology |
| Zdroj: | The Journal of Immunology. 197:4079-4089 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Menin, a tumor suppressor protein, is encoded by the MEN1 gene in humans. Certain germinal mutations of MEN1 induce an autosomal-dominant syndrome that is characterized by concurrent parathyroid adenomas and several other tumor types. Although menin is also expressed in hematopoietic lineages, its role in CD8+ T cells remains unclear. We generated Meninflox/flox CD4-Cre (Menin-KO) mice by crossing Meninflox/flox mice with CD4-Cre transgenic (Tg) mice to determine the role of menin in CD8+ T cells. Wild-type (WT) and Menin-KO mice were infected with Listeria monocytogenes expressing OVA to analyze the immune response of Ag-specific CD8+ T cells. Menin deficiency resulted in an impaired primary immune response by CD8+ T cells. On day 7, there were fewer Menin-KO OVA-specific CD8+ T cells compared with WT cells. Next, we adoptively transferred WT and Menin-KO OT-1 Tg CD8+ T cells into congenic recipient mice and infected them with L. monocytogenes expressing OVA to determine the CD8+ T cell–intrinsic effect. Menin-KO OT-1 Tg CD8+ T cells were outcompeted by the WT cells upon infection. Increased expression of Blimp-1 and T-bet, cell cycle inhibitors, and proapoptotic genes was observed in the Menin-KO OT-1 Tg CD8+ T cells upon infection. These data suggest that menin inhibits differentiation into terminal effectors and positively controls proliferation and survival of Ag-specific CD8+ T cells that are activated upon infection. Collectively, our study uncovered an important role for menin in the immune response of CD8+ T cells to infection. |
| Databáze: | OpenAIRE |
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