Cutting Edge: Viral Infection Breaks NK Cell Tolerance to “Missing Self”
Open Access
- 1 December 2008
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 181 (11), 7453-7457
- https://doi.org/10.4049/jimmunol.181.11.7453
Abstract
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 β2-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-γ 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.Keywords
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