title: Viral infection transiently reverses activation receptor-mediated NK cell hyporesponsiveness in an MHC class I-independent mechanism.
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.
authors: Department of Medicine, Gastroenterology Division, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors: Budhaditya
authors: B
authors: Mazumdar
authors: Fred D
authors: FD
authors: Bolanos
authors: Sandeep K
authors: SK
authors: Tripathy
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000008:administration & dosage; D018664:Interleukin-12 / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008024:Ligands; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D051379:Mice; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D015395:Histocompatibility Antigens Class I; C527096:Klra8 protein, mouse; D008024:Ligands; D055650:NK Cell Lectin-Like Receptor Subfamily A; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D016899:Interferon-beta