Autologous Anti-H3.3K27M TCR-expressing T-cells(Parker Institute for Cancer Immunotherapy)/(The V Foundation)

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 × 106 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.