Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection.
NKT cells are specialized cells of the immune system that bear both T cell and NK cell markers. Classical NKT cells display TCRs of restricted heterogeneity (Valpha14-Jalpha281) and recognize lipid antigens (e.g., alpha-galactosyl ceramide) presented by nonpolymorphic CD1 molecules. Recently, other nonclassical NKT subsets have been recognized, including NKT cells not reactive with CD1d-alpha-galactosyl ceramide complexes. The biological functions of these cells are unknown. Here, we show that nonclassical NKT cells that are CD1d restricted but nonreactive to alpha-GalCer are activated in response to hepatocytes expressing hepatitis B viral antigens in a transgenic mouse model of acute hepatitis B virus infection. Our results document the first in vivo function for such nonclassical NKT cells and suggest a role for these cells in the host response to HBV infection.
Baron
Jody L
JL
Department of Microbiology/Immunology, Howard Hughes Medical Institute, University of California Medical Center, San Francisco, CA 94143, USA.
Gardiner
Leon
L
Nishimura
Stephen
S
Shinkai
Kanade
K
Locksley
Richard
R
Ganem
Don
D
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology; D055610:Antigens, CD1d; D000956:Antigens, Viral / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019076:Transgenes; D014779:Virus Replication
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000956:Antigens, Viral; C526877:CD1D protein, human; D005699:Galactosylceramides; D006513:Hepatitis B e Antigens; D018398:Homeodomain Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein