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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
Author(s) -
Kobayashi Makiko,
Kobayashi Hiroyuki,
Mori Kazuya,
Pollard Richard B,
Suzuki Fujio
Publication year - 1998
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.1998.00736.x
Subject(s) - cytotoxic t cell , cd8 , biology , cytokine , cd28 , candida albicans , microbiology and biotechnology , herpes simplex virus , t cell , adoptive cell transfer , interleukin 21 , il 2 receptor , immunology , immune system , in vitro , virus , biochemistry
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 CD8 + CD11b + TCRγ/δ + 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 × 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 + TCRα/β + 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 μg/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.