Reduced MCMV Δm157 viral clearance in the absence of TSAd

Sci Rep. 2015 Mar 18:5:9219. doi: 10.1038/srep09219.

Abstract

The T cell specific adapter protein (TSAd) is expressed in activated T cells and NK cells. While TSAd is beginning to emerge as a critical regulator of Lck and Itk activity in T cells, its role in NK cells has not yet been explored. Here we have examined susceptibility to virus infections in a murine model using various viral infection models. We report that TSAd-deficient mice display reduced clearance of murine cytomegalovirus (MCMV) that lack the viral MHC class I homologue m157, which is critical for Ly49H-mediated NK cell recognition of infected cells. In this infection model, NK cells contribute in the early stages of the disease, whereas CD8+ T cells are critical for viral clearance. We found that mice infected with MCMV Δm157 displayed reduced viral clearance in the spleen as well as reduced proliferation in spleen NK cells and CD8+ T cells in the absence of TSAd. Though no other immunophenotype was detected in the infection models tested, these data suggests that in the absence of the Ly49H ligand activation, NK cell and CD8+ T cell responses may be compromised in TSAd-deficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • CD11b Antigen / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Cell Proliferation
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / veterinary
  • Cytomegalovirus Infections / virology
  • Disease Models, Animal
  • Flow Cytometry
  • Genotype
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muromegalovirus / genetics*
  • Muromegalovirus / physiology
  • Mutation
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / virology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Viral Load
  • Viral Proteins / genetics*
  • Virus Replication

Substances

  • Adaptor Proteins, Signal Transducing
  • CD11b Antigen
  • Sh2d2a protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Viral Proteins