Role of CD1d in coxsackievirus B3-induced myocarditis.
The myocarditic (H3) variant of Coxsackievirus B3 (CVB3) causes severe myocarditis in BALB/c mice and BALB/c mice lacking the invariant J alpha 281 gene, but minimal disease in BALB/c CD1d(-/-) animals. This indicates that CD1d expression is important in this disease but does not involve the invariant NKT cell often associated with CD1d-restricted immunity. The H3 variant of the virus increases CD1d expression in vitro in neonatal cardiac myocytes whereas a nonmyocarditic (H310A1) variant does not. V gamma 4(+) T cells show increased activation in both H3-infected BALB/c and J alpha 281(-/-) mice compared with CD1d(-/-) animals. The activated BALB/c V gamma 4(+) T cells from H3-infected mice kill H3-infected BALB/c myocytes and cytotoxicity is blocked with anti-CD1d but not with anti-MHC class I (K(d)/D(d)) or class II (IA/IE) mAbs. In contrast, H3 virus-infected CD1d(-/-) myocytes are not killed. These studies demonstrate that CD1d expression is essential for pathogenicity of CVB3-induced myocarditis, that CD1d expression is increased early after infection in vivo in CD1d(+) mice infected with the myocarditic but not with the nonmyocarditic CVB3 variant, and that V gamma 4(+) T cells, which are known to promote myocarditis susceptibility, appear to recognize CD1d expressed by CVB3-infected myocytes.
Huber
Sally
S
Department of Pathology, University of Vermont, Burlington, VT 05446, USA. Sally.Huber@uvm.edu
Sartini
Danielle
D
Exley
Mark
M
D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D055610:Antigens, CD1d; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D029822:Enterovirus B, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D032342:Muscle Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009205:Myocarditis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018949:Antigens, CD1; D055610:Antigens, CD1d; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta