Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8 + T-cell immunity

Academic Article

Abstract

  • Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease.Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus.NK cell-deficient (Nfil3 -/-, E4BP4 -/-)mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILEinfected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore,we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection.
  • Digital Object Identifier (doi)

    Author List

  • Lang PA; Lang KS; Xu HC; Grusdat M; Parish IA; Recher M; Elford AR; Dhanji S; Shaabani N; Tran CW
  • Start Page

  • 1210
  • End Page

  • 1215
  • Volume

  • 109
  • Issue

  • 4