Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression le...Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression levels of CD8^(+)T cells in the decidua,peripheral blood,and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry.Decidual CD8^(+)T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression.The placental CEACAM1 protein expression was analyzed using immunohistochemistry.Results:Tim-3^(+)CD8^(+)T cells were more abundant in the decidua than in the peripheral blood.Tim-3 expression in the decidual CD8^(+)T cells was significantly lower in PE patients.Decidual Tim-3^(+)CD8^(+)T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ,but lower levels of the Th2-type cytokine IL-4.CEACAM1 altered the CD107a,IFN-γ,and IL-4 levels;this was reversed by anti-Tim-3 antibodies.The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs.Conclusions:Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE,accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8^(+)T cells.展开更多
Spondyloarthropathies(SpA) are commonly observed extra-intestinal manifestations of both Crohn's disease(CD) and ulcerative colitis(UC), the two major forms of inflammatory bowel diseases(IBD).However, the immunol...Spondyloarthropathies(SpA) are commonly observed extra-intestinal manifestations of both Crohn's disease(CD) and ulcerative colitis(UC), the two major forms of inflammatory bowel diseases(IBD).However, the immunological link between these two clinical entities is still poorly understood.Several lines of evidence indicate that SpA may originate from the relocation to the joints of the immune process primarily induced in the gut.The transfer of the intestinal inflammatory process into the joints implicates that immune cells activated in the gut-draining lymph nodes can localize, at a certain point of the intestinal disease, either into the gut or into the joints.This is indicated by the over-lapping expression of adhesion molecules observed on the surface of intestinal and synovial endothelial cells during inflammation.Moreover bacterial antigens and HLA-B27 expression may be implicated in the reactivation of T cells at the articular level.Finally, accumulating evidence indicates that a T helper 17 cell-mediated immune response may contribute to IBD and IBD-related SpA with a crucial role played by tumor necrosis factor-α in CD and to a lesser extent in UC.展开更多
基金National Natural Science Foundation of China(31700799,31970859,81601311,and 81630036)Shanghai Sailing Program(17YF1411600)+2 种基金Training Program for Young Talents of the Shanghai Health System(2018YQ07)Shanghai Chenguang Program(18CG09)Development Fund of Shanghai Talents(2018110)。
文摘Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression levels of CD8^(+)T cells in the decidua,peripheral blood,and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry.Decidual CD8^(+)T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression.The placental CEACAM1 protein expression was analyzed using immunohistochemistry.Results:Tim-3^(+)CD8^(+)T cells were more abundant in the decidua than in the peripheral blood.Tim-3 expression in the decidual CD8^(+)T cells was significantly lower in PE patients.Decidual Tim-3^(+)CD8^(+)T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ,but lower levels of the Th2-type cytokine IL-4.CEACAM1 altered the CD107a,IFN-γ,and IL-4 levels;this was reversed by anti-Tim-3 antibodies.The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs.Conclusions:Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE,accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8^(+)T cells.
文摘Spondyloarthropathies(SpA) are commonly observed extra-intestinal manifestations of both Crohn's disease(CD) and ulcerative colitis(UC), the two major forms of inflammatory bowel diseases(IBD).However, the immunological link between these two clinical entities is still poorly understood.Several lines of evidence indicate that SpA may originate from the relocation to the joints of the immune process primarily induced in the gut.The transfer of the intestinal inflammatory process into the joints implicates that immune cells activated in the gut-draining lymph nodes can localize, at a certain point of the intestinal disease, either into the gut or into the joints.This is indicated by the over-lapping expression of adhesion molecules observed on the surface of intestinal and synovial endothelial cells during inflammation.Moreover bacterial antigens and HLA-B27 expression may be implicated in the reactivation of T cells at the articular level.Finally, accumulating evidence indicates that a T helper 17 cell-mediated immune response may contribute to IBD and IBD-related SpA with a crucial role played by tumor necrosis factor-α in CD and to a lesser extent in UC.
