Cutting edge: viral infection breaks NK cell tolerance to "missing self".
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.
Sun
Joseph C
JC
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
Lanier
Lewis L
LL
D000818:Animals; D016026:Bone Marrow Transplantation; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000235:genetics / Q000276:immunology*; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; C527096:Klra8 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A; D001613:beta 2-Microglobulin; D007371:Interferon-gamma