Cutting edge: viral infection breaks NK cell tolerance to "missing self"

J Immunol. 2008 Dec 1;181(11):7453-7. doi: 10.4049/jimmunol.181.11.7453.


NK cells attack cells lacking MHC class I, yet MHC class I-deficient mice have normal numbers of NK cells with intact, albeit diminished, functions. Moreover, wild-type NK cells are tolerant of MHC class I-deficient cells in mixed bone marrow chimeras. In this study, we investigated how the absence of MHC class I affects NK cells. NK cells from beta(2)-microglobulin-deficient (B2m(-/-)) and wild-type mice exhibit similar phenotypic and functional characteristics. Both B2m(-/-) and wild-type Ly49H(+) NK cells proliferated robustly and produced IFN-gamma after infection with mouse CMV. NK cells in mixed wild-type:B2m(-/-) chimeric mice were initially tolerant of MHC class I-deficient host cells. However, this tolerance was gradually lost over time and after mouse CMV infection was rapidly broken, with a pronounced rejection of host B2m(-/-) hematopoietic cells. Thus, although NK cells can be held in check against "missing self," acute inflammation driven by infection can rapidly break established self-tolerance.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Immune Tolerance* / genetics
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Knockout
  • Muromegalovirus / immunology*
  • NK Cell Lectin-Like Receptor Subfamily A / genetics
  • NK Cell Lectin-Like Receptor Subfamily A / immunology*
  • Transplantation Chimera / genetics
  • Transplantation Chimera / immunology
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / immunology*


  • Histocompatibility Antigens Class I
  • Klra8 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily A
  • beta 2-Microglobulin
  • Interferon-gamma