Atopy Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
Atopy Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Advanced Research Institute for Health Science, Juntendo University, Tokyo, Japan.
Transpl Immunol. 2021 Aug;67:101405. doi: 10.1016/j.trim.2021.101405. Epub 2021 May 8.
Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model.
We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity. We also compared the ability of syngeneic monocytic MDSCs (Mo-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) to inhibit graft rejection and investigated the suppression mechanisms.
Both syngeneic and allogeneic donor- or allogeneic third-party-derived BM-MDSCs prolonged graft survival, although syngeneic BM-MDSCs inhibited anti-donor immune responses most effectively in vitro. Syngeneic Mo-MDSCs, rather than PMN-MDSCs, were responsible for immune suppression through downregulating inducible nitric oxide synthase (iNOS) and expanded naturally occurring thymic originated Treg (nTreg) in vitro. Adoptive transfer of Mo-MDSCs, but not PMN-MDSCs, prolonged graft survival and increased Treg infiltration into the graft heart.
Recipient-derived Mo-MDSCs are most effective in prolonging graft survival via inhibiting T cell response and nTreg infiltration.
髓系来源的抑制细胞（MDSCs）和调节性 T 细胞（Tregs）是诱导免疫耐受的有吸引力的免疫细胞。为了探索提高 MDSC 治疗效果的策略，我们在小鼠心脏移植模型中研究了几种类型的 MDSC 过继转移对移植物排斥的影响。
我们分析了诱导同基因和同种异体骨髓来源的 MDSCs（BM-MDSCs）对移植物存活和抑制能力的影响。我们还比较了同基因单核细胞来源的 MDSCs（Mo-MDSCs）和多形核 MDSCs（PMN-MDSCs）抑制移植物排斥的能力，并研究了抑制机制。
同基因和异基因供体或异基因第三方来源的 BM-MDSCs 均延长了移植物存活时间，尽管同基因 BM-MDSCs 在体外最有效地抑制了抗供体免疫反应。同基因 Mo-MDSCs 而不是 PMN-MDSCs 通过下调诱导型一氧化氮合酶（iNOS）和体外扩增天然胸腺起源的调节性 T 细胞（nTreg）来发挥免疫抑制作用。Mo-MDSCs 的过继转移而不是 PMN-MDSCs 的过继转移延长了移植物存活时间，并增加了 Treg 浸润到移植物心脏。
通过抑制 T 细胞反应和 nTreg 浸润，受体来源的 Mo-MDSCs 是延长移植物存活时间最有效的方法。
