title: 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.
authors.affiliation: Department of Pathology, University of Vermont, Burlington, Vermont 05446, USA. Sally.Huber@uvm.edu
authors.forename: Sally Ann
authors.initials: SA
authors.lastname: Huber
authors.forename: Brian
authors.initials: B
authors.lastname: Roberts
authors.forename: Mohamad
authors.initials: M
authors.lastname: Moussawi
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Boyson
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D003384:Coxsackievirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D029822:Enterovirus B, Human / Q000187:drug effects / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology; D006239:Haplotypes / Q000235:genetics*; D006505:Hepatitis / Q000150:complications / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000097:blood / Q000150:complications / Q000276:immunology / Q000473:pathology*; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D011110:Polymorphism, Genetic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019210:Troponin I / Q000097:blood; D019562:Viral Load / Q000276:immunology
chemical_list: D015703:Antigens, CD; D005699:Galactosylceramides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011956:Receptors, Cell Surface; D019210:Troponin I; C493154:alpha-galactosylceramide; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D000410:Alanine Transaminase