[Schistosoma japonicum heat shock protein 60 enhances regulatory T cell immunosuppressive function by promoting the expressions of IL-10 and TGF-ß].

OBJECTIVE: To explore the possible mechanisms by which Schistosoma japonicum heat shock protein 60 (SjH-SP60) enhances CD4+CD25+ regulatory T cell (Treg) immunosuppressive function. METHODS: An in vitro method was used to investigate the effect of SjHSP60 on Treg immunosuppressive activity. Co-cultures in transwells and in vitro suppression assay were performed to investigate how SjHSP60 enhanced the immunosuppressive function of Tregs. Intracellular cytokine staining combined with flow cytometry was used to detect Treg-expressing IL-10 and TGF-ß, and flow cytometry was also used to analyze the expressions of Foxp3 and CTLA-4 in Tregs. RESULTS: SjHSP60 enhanced the immunosuppressive function of Tregs. Soluble cytokines IL-10 and TGF-ß mediated inhibitory activity of SjHSP60-triggered Tregs. SjHSP60 induced significant increases in both IL-10 and TGF-ß expressions of Tregs. Further investigation showed significant increased Foxp3 and CTLA-4 in SjHSP60-trggered Tregs. CONCLUSIONS: SjHSP60 enhances Treg immunosuppressive function by promoting the expressions of IL-10 and TGF-ß, possibly due to SjHSP60-mediated induction of Foxp3 and CTLA-4 in Tregs.

[Effects of glycolytic pathway on generation of regulatory T cells during Schistosoma japonicum infection].

OBJECTIVE: To assess the influence of glycolytic pathway on the proportion and numbers of regulatory T cells during Schistosoma japonicum infection. METHODS: A S. japonicum -infected mouse model was established, and C57/BL6 male mice infected with S. japonicum were subjected to intraperitoneal injections of with the glycolytic inhibitor 2-Deoxy-D-glucose (2DG) or PBS for 6 times, and then the cells from spleen or mesenteric lymph nodes (LNs) were isolated and analyzed by flow cytometry (FCM) to detect the percentage of Glut1+CD4+ T cells and Treg cells. RESULTS: The proportions of Glut1+CD4+ T cells in the spleen (43.58%±2.50% vs. 21.15%±0.96%; t = 8.834, P < 0.01) and mesenteric LNs (38.97%±1.97% vs. 28.40%±2.11%; t = 3.662, P < 0.05) were higher in the normal mice than those in the infected mice, and the percentages of Treg cells in the spleen (6.83%±0.21% vs. 13.30%±0.35%; t = 15.65, P < 0.01) and LNs (8.26%±0.15% vs. 14.37%±0.44%; t = 13.14, P < 0.01) were lower in the normal mice than those in the infected mice. In addition, the proportions of Treg cells in the spleen (15.50%±0.76% vs. 13.07%±0.15%; t = 3.130, P < 0.05) and LNs (17.00% ±0.41% vs. 13.83%±0.18%; t = 6.947, P < 0.01) were higher in the infected mice injected intraperitoneally with 2DG than those in the infected mice injected intraperitoneally with PBS. CONCLUSIONS: Glycolytic pathway inhibits Treg differentiation in the spleen and mesenteric LNs of S. japonicum-infected mice.

[Study on role of TIGIT signal in Th1/Th2 balance in Schistosoma japonicum-infected mice].

OBJECTIVE: To investigate the role of TIGIT signal in Th1/Th2 balance in the process of Schistosoma japonicum infection. METHODS: Male C57BL/6 mice were infected with cercariae of S. japonicum, and normal uninfected mice served as the controls. The percentages of TIGIT+ cells, Ki67+CD3+CD4+TIGIT+ cells, Ki67+CD3+CD4+TIGIT- cells, IFN-γ+CD3+CD4+TIGIT+ cells, IFN-γ+CD3+CD4+TIGIT- cells, IL-4+CD3+CD4+TIGIT+ cells and IL-4+CD3+CD4+TIGIT- cells were evaluated in mouse spleen by flow cytometry. RESULTS: The proportion of TIGIT+CD4+ T cells was higher in the spleen of S. japonicum-infected mice than in the normal uninfected mice (29.30%±0.70% vs. 3.09%±0.50%; t = 8.834, P < 0.01) . However, no significant difference in the percentages of TIGIT+ CD8+ T cells between the infection group and normal controls (3.61%±0.26% vs. 3.58%±0.16%; t = 0.108, P > 0.05), and no significant difference was detected in the percentages of TIGIT+ cells in non-T cells between the infection group and controls (1.86%±0.19% vs.1.37%±0.17%; t = 1.931, P > 0.05) . In addition, the proportion of Ki67 in the TIGIT+ cells was higher than that in the TIGIT- cells (17.03%±0.64% vs. 6.59%±0.37%; t = 14.09, P < 0.01) . The Th2/Th1 ratio was higher in the TIGIT+CD4+ T cells than in the TIGIT-CD4+ T cells (39.28%±3.75% vs. 11.79%±1.64%; t = 6.721, P < 0.01) . CONCLUSIONS: The TIGIT signaling may be involved in the development of Th2 responses in the mice infected with S. japonicum.