Impaired clearance of herpes simplex virus type 1 from mice lacking CD1d or NKT cells expressing the semivariant V alpha 14-J alpha 281 TCR.
Ag-presenting molecule CD1 and CD1-restricted NKT cells are known to contribute to defense against a range of infectious pathogens, including some viruses. CD1-restricted NKT cells, a distinct subpopulation of T cells, have striking and rapid effector functions that contribute to host defense, including rapid production of IFN-gamma and IL-4, and activation of NK cells. Consideration of the important contributions of innate and adaptive immunity to clearance of HSV prompted us to investigate the role of CD1 and of NKT cells expressing the V alpha 14-J alpha 281 TCR in the pathogenesis of HSV infection. To address this issue, we compared infection in wild-type mice with that in CD1 gene knockout (GKO) and J alpha 281 GKO mice. In this study, we report impaired clearance of virus and viral Ags, and more florid acute infection in mice lacking CD1 (and by inference, CD1-restricted T cells), in comparison with parental C57BL6 mice. In J alpha 281 GKO mice there was also impairment of virus clearance, resembling that seen in CD1 GKO mice. These results imply roles for the V alpha 14-J alpha 281 subset of NKT cells and for CD1d in control of HSV infection.
Grubor-Bauk
Branka
B
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide, SA, Australia.
Simmons
Anthony
A
Mayrhofer
Graham
G
Speck
Peter G
PG
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics*; D055610:Antigens, CD1d; D000956:Antigens, Viral / Q000378:metabolism; D017950:Ganglia, Sensory / Q000276:immunology / Q000821:virology; D014644:Genetic Variation / Q000276:immunology; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D019562:Viral Load; D017735:Virus Latency / Q000235:genetics / Q000276:immunology
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000956:Antigens, Viral; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta