Viral infection transiently reverses activation receptor-mediated NK cell hyporesponsiveness in an MHC class I-independent mechanism

Budhaditya Mazumdar, Fred D. Bolanos, Sandeep K. Tripathy

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Continuous engagement of the Ly49H activating receptor with its ligand (m157) in a transgenic mouse expressing m157 (m157-Tg) results in hyporesponsiveness of Ly49H+ NK cells. The same interaction, during murine cytomegalovirus (MCMV) infection, leads to activation of Ly49H+ NK cells. MCMV infection results in decreased MHC class I (MHC-I) expression on the infected cell as well as inflammatory responses, both of which do not take place in the uninfected m157-Tg mouse, potentially allowing for activation of NK cells in the context of MCMV infection. In this study, we demonstrated that viral infection transiently reverses activation receptor-mediated NK cell hyporesponsiveness in an MHC-I-independent mechanism. Furthermore, Ly49H+ NK cells in an MHC-I-deficient environment remained hyporesponsive in the context of m157 expression, even when mature WT splenocytes were transferred into m157-Tg mice in an MHC-I-deficient environment. However, the administration of cytokines TNF-α, IL-12, and IFN-β resulted in a partial recovery from activation receptor-induced hyporesponsiveness. Thus, the release of the aforementioned cytokines during MCMV infection and not the downregulation of MHC-I expression appears to be responsible for partial resolution of Ly49H receptor-induced NK cell hyporesponsiveness.

Original languageEnglish
Pages (from-to)1345-1355
Number of pages11
JournalEuropean Journal of Immunology
Volume43
Issue number5
DOIs
StatePublished - Apr 1 2013

Keywords

  • Activating receptor
  • NK cell
  • NK cell ligand
  • Tolerance

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