Menin Plays a Critical Role in the Regulation of the Antigen-Specific CD8+ T Cell Response upon Listeria Infection

J Immunol. 2016 Nov 15;197(10):4079-4089. doi: 10.4049/jimmunol.1502295. Epub 2016 Oct 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology*
  • Listeriosis / microbiology
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • T-Box Domain Proteins / genetics
  • Transcription Factors / genetics


  • Men1 protein, mouse
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Ovalbumin
  • Positive Regulatory Domain I-Binding Factor 1