
免疫チェックポイント分子であるPD-1は、T細胞の活性化を抑制するだけでなく、Th2細胞への分化を強く抑制することでアレルギー性炎症を制御する可能性を持つ。


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Programmed Cell Death Protein-1 (PD-1) represents endogenous mechanisms of negative immunoregulation. While the modulation of effector functions has been the major focus of PD-1 research, quick PD-1 upregulation in naïve T cells starting 1 h after priming raised a possibility that PD-1 also affects the development of effector T cells. The role of PD-1 in functional differentiation into Th1 and Th2 has been unclear. In murine naïve CD4+ T cell activation, we found that PD-1 stimulation during the early stage of T cell activation strongly impaired Th2 cell development, while Th1 cell induction was relatively resistant to this immunosuppressive signaling. The steep decline in Th2 cell induction suggested the significance of PD-1 in allergic inflammation. Treatment with anti-human PD-1 agonist antibody inhibited allergic inflammation in human PD-1-knock-in mice as shown by the reduction of Th2 cells, IgE levels and eosinophilic infiltration. This study shows that PD-1 regulates not only the intensity but also the quality of immune response by deviating Th differentiation. PD-1 stimulators are projected to be valuable in suppressing various forms of inflammatory activities, but the efficacy against Th2-dominant immune response may be particularly high.

### Competing Interest Statement

M.T., K.S., Y.T., T.H. and A.O. are inventors on patent applications (WO2021/241523A1, WO2022/239820) submitted by Foundation for Biomedical Research and Innovation at Kobe, National Institutes of Biomedical Innovation, Health and Nutrition, and Meiji Seika Pharma Co. Ltd. that cover anti-human PD-1 agonist antibodies and their therapeutic application. K.S. and Y.T. are employees of Meiji Seika Pharma Co. Ltd. The remaining authors declare no competing interests.

PD-1はTh2細胞へのヘルパーT細胞分化を負に制御する