Vitalant Research Institute, San Francisco, CA; and.
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA.
Blood Adv. 2020 Nov 10;4(21):5547-5561. doi: 10.1182/bloodadvances.2020002867.
Alloimmunization against platelet-rich plasma (PRP) transfusions can lead to complications such as platelet refractoriness or rejection of subsequent transfusions and transplants. In mice, pathogen reduction treatment of PRP with UVB light and riboflavin (UV+R) prevents alloimmunization and appears to induce partial antigen-specific tolerance to subsequent transfusions. Herein, the in vivo responses of antigen-presenting cells and T cells to transfusion with UV+R-treated allogeneic PRP were evaluated to understand the cellular immune responses leading to antigen-specific tolerance. Mice that received UV+R-treated PRP had significantly increased transforming growth factor β (TGF-β) expression by CD11b+ CD4+ CD11cHi conventional dendritic cells (cDCs) and CD11bHi monocytes (P < .05). While robust T-cell responses to transfusions with untreated allogeneic PRP were observed (P < .05), these were blocked by UV+R treatment. Mice given UV+R-treated PRP followed by untreated PRP showed an early significant (P < .01) enrichment in regulatory T (Treg) cells and associated TGF-β production as well as diminished effector T-cell responses. Adoptive transfer of T-cell-enriched splenocytes from mice given UV+R-treated PRP into naive recipients led to a small but significant reduction of CD8+ T-cell responses to subsequent allogeneic transfusion. These data demonstrate that pathogen reduction with UV+R induces a tolerogenic profile by way of CD11b+ CD4+ cDCs, monocytes, and induction of Treg cells, blocking T-cell activation and reducing secondary T-cell responses to untreated platelets in vivo.
针对富含血小板血浆 (PRP) 输血的同种异体免疫反应可导致血小板反应性降低或随后的输血和移植排斥等并发症。在小鼠中，用紫外线 B 光和核黄素 (UV+R) 对 PRP 进行病原体减少处理可预防同种异体免疫反应，并似乎可诱导对随后输血的部分抗原特异性耐受。在此，评估了抗原呈递细胞和 T 细胞对用 UV+R 处理的同种异体 PRP 输血的体内反应，以了解导致抗原特异性耐受的细胞免疫反应。接受 UV+R 处理的 PRP 输血的小鼠，其 CD11b+ CD4+ CD11cHi 常规树突状细胞 (cDC) 和 CD11bHi 单核细胞中的转化生长因子 β (TGF-β) 表达显著增加（P <.05）。虽然观察到未处理的同种异体 PRP 输血会引起强烈的 T 细胞反应（P <.05），但这种反应会被 UV+R 处理阻断。给予 UV+R 处理的 PRP 随后给予未处理的 PRP 的小鼠表现出早期显著的（P <.01）调节性 T (Treg) 细胞和相关 TGF-β 产生的富集，以及效应 T 细胞反应的减弱。从接受 UV+R 处理的 PRP 的小鼠中分离出富含 T 细胞的脾细胞并转移到未致敏的受体中，可导致随后对同种异体输血的 CD8+ T 细胞反应略有降低。这些数据表明，用 UV+R 进行病原体减少处理可通过 CD11b+ CD4+ cDC、单核细胞和 Treg 细胞的诱导来诱导耐受表型，从而阻断 T 细胞激活并减少体内未处理血小板的继发性 T 细胞反应。
