CD4⁺ T cells induced from human iPSCs (iCD4⁺ T cells) offer a therapeutic opportunity for overcoming immune pathologies arising from hematopoietic stem cell transplantation. However, most iCD4⁺ T cells are conventional helper T cells, which secrete inflammatory cytokines. We induced high-level expression of FOXP3, a master transcription factor of regulatory T cells, in iCD4⁺ T cells. Human iPSC-derived, FOXP3-induced CD4⁺ T (iCD4⁺ Treg-like) cells did not secrete inflammatory cytokines upon activation. Moreover, they showed demethylation of the Treg-specific demethylation region, suggesting successful conversion to immunosuppressive iCD4⁺ Treg-like cells. We further assessed these iCD4⁺ Treg-like cells for CAR-mediated immunosuppressive ability. HLA-A2 CAR-transduced iCD4⁺ Treg-like cells inhibited CD8⁺ cytotoxic T cell (CTL) division in a mixed lymphocyte reaction assay with A2⁺ allogeneic CTLs and suppressed xenogeneic graft-versus-host disease (GVHD) in NSG mice treated with A2⁺ human PBMCs. In most cases, these cells suppressed the xenogeneic GvHD progression as much as natural CD25⁺CD127⁻ Tregs did.

由人 iPSC 诱导的 CD4 ⁺ T 细胞（iCD4 ⁺ T 细胞）为克服造血干细胞移植引起的免疫病理提供了治疗机会。然而，大多数 iCD4 ⁺ T 细胞是传统的辅助 T 细胞，可分泌炎症细胞因子。我们在 iCD4 ⁺ T 细胞中诱导了 FOXP3（调节性 T 细胞的主要转录因子）的高水平表达。人 iPSC 衍生的 FOXP3 诱导的 CD4 ⁺ T（iCD4 ⁺ Treg 样）细胞在激活后不分泌炎症细胞因子。此外，他们显示出 Treg 特异性去甲基化区域的去甲基化，表明成功转化为免疫抑制性 iCD4 ⁺ Treg 样细胞。我们进一步评估了这些 iCD4 ⁺ Treg 样细胞的 CAR 介导的免疫抑制能力。在 A2 ⁺ 同种异体混合淋巴细胞反应测定中，HLA-A2 CAR 转导的 iCD4 ⁺ Treg 样细胞抑制 CD8 ⁺ 细胞毒性 T 细胞 (CTL) 分裂用 A2 ⁺ 人 PBMC 处理的 NSG 小鼠中的 CTL 和抑制的异种移植物抗宿主病 (GVHD)。在大多数情况下，这些细胞与天然 CD25 ⁺ CD127 ⁻ Tregs 一样抑制异种 GvHD 进展。