Protective role of Fas-FasL signaling in lethal infection with herpes simplex virus type 2 in mice.
Herpes simplex virus type 2 (HSV-2) induces acute local infection followed by latent infection in the nervous system and often leads to the development of lethal encephalitis in immunocompromised hosts. The mechanisms of immune protection against lethal HSV-2 infection, however, have not been clarified. In this study, we examined the roles of Fas-Fas ligand (FasL) signaling in lethal infection with HSV-2 by using mice with mutated Fas (lpr) or FasL (gld) in C57BL/6 background. Both lpr and gld mice exhibited higher mortality than wild-type (WT) C57BL/6 mice after infection with virulent HSV-2 strain 186 and showed significantly increased viral titers in the spinal cord compared with WT mice 9 days after infection, just before the mice started to die. There were no differences in the numbers of CD4+ and CD8+ T cells infiltrated in the spinal cord or in the levels of HSV-2-specific gamma interferon produced by those cells in a comparison of lpr and WT mice 9 days after infection. Adoptive transfer studies demonstrated that CD4+ T cells from WT mice protected gld mice from lethal infection by HSV-2. Furthermore, CD4+ T cells infiltrated in the spinal cord of HSV-2-infected WT mice expressed functional FasL that induced apoptosis of Fas-expressing target cells in vitro. These results suggest that FasL-mediated cytotoxic activity of CD4+ T cells plays an important role in host defense against lethal infection with HSV-2.
Ishikawa
Takahiro
T
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Yamada
Hisakata
H
Oyamada
Akiko
A
Goshima
Fumi
F
Nishiyama
Yukihiro
Y
Yoshikai
Yasunobu
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D053222:Fas Ligand Protein / Q000502:physiology*; D005260:Female; D006561:Herpes Simplex / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; D019014:fas Receptor