NK cell-mediated lysis of autologous HCMV-infected skin fibroblasts is highly variable among NK cell clones and polyclonal NK cell lines

Clin Immunol. 2002 Nov;105(2):126-40. doi: 10.1006/clim.2002.5273.

Abstract

Lysis of human cytomegalovirus (HCMV)-infected fibroblasts by autologous natural killer (NK) cells was examined in vitro. For NK cell clones, receptor expression was determined at the level of mRNA and cell-surface protein and compared to the lysis of HCMV AD169 strain-infected fibroblasts in which HLA class I was >70% downregulated. The clones ranged broadly in their ability to lyse AD169-infected fibroblasts, correlating neither with the expression of inhibitory KIR, leukocyte inhibitory receptor-1, or CD94:NKG2A receptors nor with the number of different inhibitory KIR expressed per clone. Some lines of polyclonal NK cells preferentially lysed AD169-infected cells and similarly lysed fibroblasts infected with mutant virus RV798, which lacks the genes for downregulating HLA class I. These results demonstrate that NK cell lysis of HCMV-infected autologous fibroblasts is more complex than a simple missing-self mechanism involving downregulation of HLA class I and failure to engage inhibitory self-specific KIR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Clone Cells
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology
  • Cytotoxicity, Immunologic
  • Down-Regulation
  • Fibroblasts / immunology
  • Fibroblasts / virology
  • Genes, Viral
  • HLA Antigens / metabolism
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • In Vitro Techniques
  • Killer Cells, Natural / immunology*
  • Mutation
  • Receptors, Immunologic / metabolism
  • Receptors, KIR
  • Skin / immunology
  • Skin / virology

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Receptors, Immunologic
  • Receptors, KIR