The RIG-I-like receptor LGP2 controls CD8(+) T cell survival and fitness

Immunity. 2012 Aug 24;37(2):235-48. doi: 10.1016/j.immuni.2012.07.004. Epub 2012 Jul 26.

Abstract

The RIG-I-like receptors (RLRs) signal innate immune defenses upon RNA virus infection, but their roles in adaptive immunity have not been clearly defined. Here, we showed that the RLR LGP2 was not essential for induction of innate immune defenses, but rather was required for controlling antigen-specific CD8(+) T cell survival and fitness during peripheral T cell-number expansion in response to virus infection. Adoptive transfer and biochemical studies demonstrated that T cell-receptor signaling induced LGP2 expression wherein LGP2 operated to regulate death-receptor signaling and imparted sensitivity to CD95-mediated cell death. Thus, LGP2 promotes an essential prosurvival signal in response to antigen stimulation to confer CD8(+) T cell-number expansion and effector functions against divergent RNA viruses, including West Nile virus and lymphocytic choriomeningitis virus.

Publication types

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

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Communication / immunology
  • Cell Survival / immunology*
  • Central Nervous System / immunology
  • Dendritic Cells / immunology
  • Humans
  • Immunity, Innate / immunology
  • Interferon-beta / immunology
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA Helicases / immunology*
  • RNA, Viral / immunology*
  • Signal Transduction / immunology
  • West Nile Fever / immunology
  • West Nile virus / immunology
  • fas Receptor / immunology

Substances

  • RNA, Viral
  • fas Receptor
  • Interferon-beta
  • Dhx58 protein, mouse
  • RNA Helicases