Blanco Tomas, Singh Rohan Bir, Nakagawa Hayate, Taketani Yukako, Dohlman Thomas H, Chen Yihe, Chauhan Sunil K, Yin Jia, Dana Reza
Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, USA.
Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, USA.
Mucosal Immunol. 2023 Oct;16(5):711-726. doi: 10.1016/j.mucimm.2022.12.002. Epub 2023 Jan 13.
Corneal transplant rejection primarily occurs because of the T helper 1 (Th1) effector cell-mediated immune response of the host towards allogeneic tissue. The evidence suggests that type 1 migratory conventional CD103 dendritic cells (CD103DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts. The immunosuppressive function of CD103DC1 has been extensively studied in non-transplantation settings. We found that host CD103DC1 infiltrates the corneal graft and migrates to the draining lymph nodes to suppress alloreactive CD4 Th1 cells via the programmed death-ligand 1 axis. The systemic depletion of CD103 DC1 in allograft recipients leads to amplified Th1 activation, impaired Treg function, and increased rate of allograft rejection. Although allograft recipient Rag1 null mice reconstituted with naïve CD4CD25 T cells efficiently generated peripheral Treg cells (pTreg), the CD103DC1-depleted mice failed to generate pTreg. Furthermore, adoptive transfer of pTreg failed to rescue allografts in CD103DC1-depleted recipients from rejection. These data demonstrate the critical role of CD103DC1 in regulating host alloimmune responses.
角膜移植排斥主要是由于宿主对同种异体组织的T辅助1（Th1）效应细胞介导的免疫反应所致。有证据表明，1型迁移性常规CD103树突状细胞（CD103DC1）在肿瘤环境中获得免疫抑制表型；然而，CD103DC1在同种异体移植存活中的作用在组织移植中仍然是一个具有重大临床意义的难以捉摸的问题。在本研究中，我们评估了CD103DC1在抑制针对移植角膜同种异体移植物的Th1同种异体反应性中的作用。CD103DC1的免疫抑制功能已在非移植环境中得到广泛研究。我们发现宿主CD103DC1浸润角膜移植物并迁移至引流淋巴结，通过程序性死亡配体1轴抑制同种异体反应性CD4 Th1细胞。同种异体移植受体中CD103 DC1的全身耗竭导致Th1激活增强、调节性T细胞（Treg）功能受损以及同种异体移植排斥率增加。尽管用幼稚CD4CD25 T细胞重建的同种异体移植受体Rag1基因敲除小鼠有效地产生了外周Treg细胞（pTreg），但CD103DC1耗竭的小鼠未能产生pTreg。此外，pTreg的过继转移未能挽救CD103DC1耗竭受体中的同种异体移植物免于排斥。这些数据证明了CD103DC1在调节宿主同种异体免疫反应中的关键作用。
