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Slam haplotype 2 promotes NKT but suppresses Vγ4+ T-cell activation in coxsackievirus B3 infection leading to increased liver damage but reduced myocarditis.

Abstract
There are two major haplotypes of signal lymphocytic activation molecule (Slam) in inbred mouse strains, with the Slam haplotype 1 expressed in C57Bl/6 mice and the Slam haplotype 2 expressed in most other commonly used inbred strains, including 129 mice. Because signaling through Slam family receptors can affect innate immunity [natural killer T cell (NKT) and γ-δ T-cell receptor], and innate immunity can determine susceptibility to coxsackievirus B3 (CVB3) infection, the present study evaluated the response of C57Bl/6 and congenic B6.129c1 mice (expressing the 129-derived Slam locus) to CVB3. CVB3-infected C57Bl/6 male mice developed increased myocarditis but reduced hepatic injury compared with infected B6.129c1 mice. C57Bl/6 mice also had increased γδ(+) and CD8(+)interferon-γ(+) cells but decreased numbers of NKT (T-cell receptor β chain + mCD1d tetramer(+)) and CD4(+)FoxP3(+) cells compared with B6.129c1 mice. C57Bl/6 mice were infected with CVB3 and treated with either α-galactosylceramide, an NKT cell-specific ligand, or vehicle (dimethyl sulfoxide/PBS). Mice treated with α-galactosylceramide showed significantly reduced myocarditis. Liver injuries, as determined by alanine aminotransferase levels in plasma, were increased significantly, confirming that NKT cells are protective for myocarditis but pathogenic in the liver.
AuthorsSally Ann Huber, Brian Roberts, Mohamad Moussawi, Jonathan E Boyson
JournalThe American journal of pathology (Am J Pathol) Vol. 182 Issue 2 Pg. 401-9 (Feb 2013) ISSN: 1525-2191 [Electronic] United States
PMID23195432 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antigens, CD
  • Galactosylceramides
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Cell Surface
  • Troponin I
  • alpha-galactosylceramide
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Alanine Transaminase
Topics
  • Adaptive Immunity (drug effects)
  • Alanine Transaminase (blood)
  • Animals
  • Antigens, CD (genetics, metabolism)
  • Coxsackievirus Infections (complications, immunology, pathology)
  • Enterovirus B, Human (drug effects, immunology)
  • Galactosylceramides (pharmacology)
  • Haplotypes (genetics)
  • Hepatitis (complications, immunology, pathology)
  • Liver (immunology, pathology, virology)
  • Lymphocyte Activation (drug effects, immunology)
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocarditis (blood, complications, immunology, pathology)
  • Natural Killer T-Cells (drug effects, immunology)
  • Polymorphism, Genetic
  • Receptors, Antigen, T-Cell, gamma-delta (immunology)
  • Receptors, Cell Surface (genetics, metabolism)
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Troponin I (blood)
  • Viral Load (immunology)

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