The regulation of burn-associated infections with herpes simplex virus type 1 or Candida albicans by a non-toxic aconitine-hydrolysate, benzoylmesaconine. Part 2: Mechanism of the antiviral action.
In the accompanying paper, the resistance to infections with HSV type 1 (HSV-1) and Candida albicans was improved in thermally injured mice treated with benzoylmesaconine (BEN), an aconitine-hydrolysate isolated from heated Aconiti tuber, or inoculated with splenic CD4+ T cells from BEN-treated mice (BEN T cells). In this paper, therefore, the antiviral mechanism of BEN T cells (or BEN) on the improved resistance of burned mice to the HSV-1 infection was studied. Burn-associated CD + CD11b+ TCRgamma/delta+ type-2 T cells have been shown to be a key on the increased susceptibility of thermally injured mice to infection with HSV-1 or C. albicans. The susceptibility of T6S-mice, mice inoculated with 1 x 10(6) cells/mouse of T6S cells (a clone of burn-associated type-2 T cells), to HSV-1 infection was similar to that of thermally injured mice. The adoptive transfer of BEN T cells to T6S-mice restores their impaired resistance to HSV-1 infection. The type-2 cytokine levels in sera of T6S-mice were decreased after inoculation of BEN T cells. BEN T cells inhibited the type-2 cytokine production by T6S cells when they were cocultured in vitro. BEN T cells, characterized as CD4+ CD28+ TCRalpha/beta+ Vicia villosa (VV) lectin-adherent T cells, showed non-specific ability to inhibit the cytokine production by various type-2 T cells. From the results of the cytokine-producing profile, BEN T cells were shown to be a different subset of CD4+ T cells from Th1 and Th2 cells, although these three CD4+ T cells had similar properties phenotypically. BEN T cells were induced in normal mice 1-4 days after the oral treatment of BEN (1 microg/kg or more). These results suggest that, through the induction of antagonistic CD4+ T cells against burn-associated type-2 T cells, BEN may improve the resistance of T6S-mice (or thermally injured mice) to the infection of HSV-1.
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0835, USA.
M
M
Kobayashi
H
H
Kobayashi
K
K
Mori
R
R
Pollard
F
F
Suzuki
D000157:Aconitine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002056:Burns / Q000150:complications / Q000382:microbiology* / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000209:etiology / Q000517:prevention & control*; D002999:Clone Cells / Q000187:drug effects / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D006561:Herpes Simplex / Q000209:etiology / Q000517:prevention & control*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D006868:Hydrolysis; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; C085283:benzoylmesaconine; D000157:Aconitine