Quiescent Tissue Stem Cells Evade Immune Surveillance

Immunity. 2018 Feb 20;48(2):271-285.e5. doi: 10.1016/j.immuni.2018.02.001.


Stem cells are critical for the maintenance of many tissues, but whether their integrity is maintained in the face of immunity is unclear. Here we found that cycling epithelial stem cells, including Lgr5+ intestinal stem cells, as well as ovary and mammary stem cells, were eliminated by activated T cells, but quiescent stem cells in the hair follicle and muscle were resistant to T cell killing. Immune evasion was an intrinsic property of the quiescent stem cells resulting from systemic downregulation of the antigen presentation machinery, including MHC class I and TAP proteins, and is mediated by the transactivator NLRC5. This process was reversed upon stem cell entry into the cell cycle. These studies identify a link between stem cell quiescence, antigen presentation, and immune evasion. As cancer-initiating cells can derive from stem cells, these findings may help explain how the earliest cancer cells evade immune surveillance.

Keywords: MHC class I; Nlrc5; T cell; antigen presentation; hair follicle; immune privilege; immunology; intestine; quiescence; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Hair Follicle / cytology*
  • Immune Evasion*
  • Immunologic Surveillance*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred C57BL
  • Muscles / cytology
  • Receptors, G-Protein-Coupled / physiology
  • Stem Cells / immunology*
  • Tumor Escape


  • Intracellular Signaling Peptides and Proteins
  • Lgr5 protein, mouse
  • NLRC5 protein, mouse
  • Receptors, G-Protein-Coupled