粒细胞性髓源抑制性细胞在日本血吸虫感染的实验过程中抑制 T 滤泡辅助细胞。
Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection.
机构信息
Key Laboratory of Parasite and Vector Biology, National Health Commission of the People's Republic of China, Shanghai, 200025, China.
Department of Pathogenic Biology, Binzhou Medical University, Yantai, Shandong, 264003, China.
出版信息
Parasit Vectors. 2021 Sep 26;14(1):497. doi: 10.1186/s13071-021-05006-8.
BACKGROUND
CD4 T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. However, the role of Tfh cells in schistosome infection is not fully understood. In this study, the dynamics and roles of Tfh cell regulation were examined. We demonstrated that granulocytic myeloid-derived suppressor cells (G-MDSC) can suppress the proliferation of Tfh cells.
METHODS
The levels of Tfh cells and two other Th cells (Th1, Th2) were quantitated at different Schistosoma japonicum infection times (0,3, 5, 8, 13 weeks) using flow cytometry. The proliferation of Tfh cells stimulated by soluble egg antigen (SEA) and soluble worm antigen (SWA) in vivo and in vitro were analyzed. Tfh cells were co-cultured with MDSC to detect the proliferation of Tfh cells labelled by 5(6)-carboxyfluorescein diacetate N-succinimidyl ester. We dynamically monitored the expression of programmed cell death protein 1 (PD-1) on the surface of Tfh cells and programmed cell death ligand 1 (PD-L1) on the surface of MDSC at different infection times (0, 3, 5, 8 weeks). Naïve CD4 T cells (in Tfh cell differentiation) were co-cultured with G-MDSC or monocytic MDSC in the presence, or in the absence, of PD-L1 blocking antibody.
RESULTS
The proportion of Tfh cells among CD4 T cells increased gradually with time of S. japonicum infection, reaching a peak at 8 weeks, after which it decreased gradually. Both SEA and SWA caused an increase in Tfh cells in vitro and in vivo. It was found that MDSC can suppress the proliferation of Tfh cells. The expression of PD-1 on Tfh cells and PD-L1 from MDSC cells increased with prolongation of the infection cycle. G-MDSC might regulate Tfh cells through the PD-1/PD-L1 pathway.
CONCLUSIONS
The reported study not only reveals the dynamics of Tfh cell regulation during S. japonicum infection, but also provides evidence that G-MDSC may regulate Tfh cells by PD-1/PD-L1. This study provides strong evidence for the important role of Tfh cells in the immune response to S. japonicum infection.
背景
CD4 T 辅助（Th）细胞在宿主体液和细胞免疫对抗寄生虫感染以及血吸虫病的免疫病理学中发挥关键作用。滤泡辅助 T（Tfh）细胞是参与抗感染免疫的一种特殊 Th 细胞亚群。然而，Tfh 细胞在血吸虫感染中的作用尚未完全阐明。在这项研究中，我们研究了 Tfh 细胞调节的动态和作用。我们证明粒细胞髓源抑制细胞（G-MDSC）可以抑制 Tfh 细胞的增殖。
方法
采用流式细胞术检测不同日本血吸虫感染时间（0、3、5、8、13 周）时 Tfh 细胞和另外两种 Th 细胞（Th1、Th2）的水平。分析体内和体外可溶性虫卵抗原（SEA）和可溶性虫体抗原（SWA）刺激 Tfh 细胞的增殖。将 Tfh 细胞与 MDSC 共培养，检测经 5（6）-羧基荧光素二乙酸琥珀酰亚胺酯标记的 Tfh 细胞的增殖。我们在不同感染时间（0、3、5、8 周）动态监测 Tfh 细胞表面程序性死亡蛋白 1（PD-1）和 MDSC 表面程序性死亡配体 1（PD-L1）的表达。在存在或不存在 PD-L1 阻断抗体的情况下，将幼稚 CD4 T 细胞（在 Tfh 细胞分化中）与 G-MDSC 或单核细胞 MDSC 共培养。
结果
日本血吸虫感染后，Tfh 细胞在 CD4 T 细胞中的比例随时间逐渐增加，在 8 周时达到高峰，随后逐渐下降。SEA 和 SWA 均可在体内和体外引起 Tfh 细胞的增加。研究发现 MDSC 可抑制 Tfh 细胞的增殖。随着感染周期的延长，Tfh 细胞和 MDSC 细胞上 PD-1 的表达增加。G-MDSC 可能通过 PD-1/PD-L1 途径调节 Tfh 细胞。
结论
本研究不仅揭示了日本血吸虫感染过程中 Tfh 细胞调节的动态变化，还提供了 G-MDSC 通过 PD-1/PD-L1 调节 Tfh 细胞的证据。该研究为 Tfh 细胞在日本血吸虫感染免疫反应中的重要作用提供了有力证据。
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