ABSTRACT
Objective To investigate the roles of inducible costimulatory molecules (ICOS) and related cytokines in the immune regulation of Echinococcus granulosus infections in mice. Methods Eighty BALB/c mice (weight 18–22 g) were divided into the control and infection groups, of 40 animals in each group. E. granulosus infection was modeled in mice by intraperitoneal injection of 10 000 protoscoleces per mouse. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and peripheral interleukin-4 (IL-4) and IL-10 levels were measured 2, 8, 30, 60, 180 days post-infection. Mouse liver specimens were excised for hematoxylin-eosin (HE) staining and immunostaining, and ICOS expression was quantified in mouse liver specimens using quantitative real-time PCR (qPCR) assay. Results There were no significant differences in serum ALT (F = 12.082, P < 0.05), AST (F = 6.347, P < 0.05) or ALP levels (F = 52.186, P < 0.05) in mice 2, 8, 30, 60 and 180 days post-infection with E. granulosus. The serum ALT levels were significantly higher in the infection group than in the control group 2 [(61.72 ± 9.89) vs. (50.65 ± 4.67)U/L, P < 0.05] and 30 days post-infection [(80.61 ± 23.71)vs.(67.75 ± 9.79)U/L, P < 0.05], and the serum ALT levels were significantly higher in the infection group than in the control group 2 [(181.06 ± 60.61) vs.(115.58 ± 17.66)U/L, P < 0.05] and 180 days post-infection [(137.84 ± 29.01) vs. (108.05 ± 10.33) U/L, P < 0.05], while greater serum ALP levels were measured in the infection group than in the control group 2 [(162.90 ± 21.04)vs.(64.54 ± 5.99)U/L, P < 0.05], 8[(176.36 ± 24.56) vs. (62.70 ± 9.21)U/L, P < 0.05] and 30 days post-infection [(138.86 ± 13.59) vs. (58.60 ± 5.28) U/L, P < 0.05]. A few inflammatory cells were seen in mouse liver in the infection group 30 days post-infection, and no apparent changes were found in the mouse hepatic structure 60 days post-infection. On day 180 post-infection, a large number of epithelium-like cells presented fibrotic growth in mouse liver in the cyst-infiltrating regions, with cuticula formation seen, and plenty of red cells were present in lesions and hepatocyte space. Positive ICOS expression was detected in mouse liver in the infection group, with ICOS-positive cells predominantly seen in the cytoplasm of the hepatocyte, and the ICOS expression increased over time. The relative ICOS mRNA expression was 2.732 ± 0.094 on day 180 post-infection, which was significantly greater than that on day 2 postinfection (0.746 ± 0.049). There were no significant differences in serum IL-4 or IL-10 levels at different time points after E. granulosus infections, while the serum IL-4 and IL-10 levels peaked in the infection group 180 days and 60 days post-infection, respectively. Higher serum IL-4 levels were measured in the infection group than in the control group 8 [(22.50 ± 3.24) vs. (5.82 ± 0.49) pg/mL, P < 0.05], 30 [(15.49 ± 4.73) vs. (5.10 ± 1.38) pg/mL, P < 0.05], 60 [(36.93 ± 6.14) vs. (4.13 ± 1.19) pg/mL, P < 0.05] and 180 days post-infection [(198.35 ± 0.70) vs. (4.19 ± 0.98) pg/mL, P < 0.05], and higher IL-10 levels were measured in the infection group than in the control group 2 [(4.84 ± 1.91) vs. (2.11 ± 1.03) pg/mL, P < 0.05], 8 [(44.72 ± 14.63) vs. (3.16 ± 0.60) pg/mL, P < 0.05], 30 [(25.47 ± 8.00) vs. (3.83 ± 1.87) pg/mL, P < 0.05], 60 [(187.16 ± 60.44) vs. (3.69 ± 1.05) pg/mL, P < 0.05] and 180 days post-infection [(85.40 ± 7.15) vs. (3.25 ± 0.93) pg/mL, P < 0.05]. Conclusions High ICOS expression is present in the liver of mice with E. granulosus infections. The positive ICOS expression and immune activation levels increase with the time of E. granulosus infections, leading to aggravation of hepatocyte injury caused by inflammation.
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Objective:To investigate the role and clinical significance of T follicular helper (Tfh) cells in the pathogenesis of eosinophilic gastroenteritis (EG) in children.Methods:A total of 17 children diagnosed with EG in the Department of Gastroenterology, Children′s Hospital of Nanjing medical University from October 2018 to January 2020 were recruited as EG group.During the same period, 15 children diagnosed with colon polyps were included as control group.Flow cytometry was used to detect Tfh cells and their functional molecules, including inducible costimulatory molecules (ICOS) and programmed cell death protein 1 (PD-1) in peripheral blood of the 2 groups.Results:The median (interquartile range) of Tfh cell frequency in peripheral blood of children with EG group was 7.3 (2.6)%, which was significantly higher than that of controls 2.8 (1.4)% ( P<0.05). There were significant differences in the median (interquartile range) of ICOS [1.5 (1.3)% vs.0.1 (0.2)%] and PD-1 expressions [1.8 (3.2)% vs.0.7 (0.6)%] on Tfh cells between children with EG group and control group (all P<0.05). The frequency of Tfh cells in the peripheral blood of children with EG was positively correlated with the expressions of ICOS ( r=0.746, P<0.05) and PD-1 ( r=0.893, P<0.05), and immunoglobulin E (IgE) level ( r=0.587, P<0.05). Conclusions:The frequency of Tfh cells in peripheral blood of children with EG significantly increases, which are proliferative and overexpressed with ICOS and PD-1.Moreover, the frequency of Tfh cells of EG patients is positively correlated with the level of IgE.The abnormal expression of Tfh cells may play a promoting role in the mechanism of EG.
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Objective To study the relationship between the co‐expression levels of inducible costimulatory molecule (ICOS)and CD28 on peripheral blood CD4+ and CD8+ T cells and Behcet’s disease(BD).Methods Flow cytometry was used to detect the expression levels of ICOS and CD28 on peripheral blood CD4+ and CD8+ T cells of BD patients(n=22) ,including those with active BD(ABD ,n= 14)and stable BD(SBD ,n= 8) ,and of normal subjects(n= 22).Results The proportion of CD28+ ICOS+ CD4+ T cells was significantly increased in ABD patients when compared with normal subjects [(34.72 ± 12.87)% vs.(25.36 ± 8.24)% ,P0.05]between the two groups.The proportions of CD28-ICOS+ CD4+ T cells and CD28-ICOS+CD8+ T cells were both obviously increased in ABD patients when compared with those in normal subjects[(2.54 ± 1.63)% vs.(0.76 ± 0.25)% for CD28- ICOS+ CD4+ T cells ,P< 0.05;(8.79 ± 3.41)% vs.(3.04 ± 1.25)% for CD28-ICOS+CD8+ T cells ,P<0.05].Conclusion The increased expression level of ICOS on peripheral blood CD4+ and CD8+ T cells is not closely associated with the expression of CD28 to some extent in BD patients ,suggesting that cells expressing only ICOS play an important role in the development of BD.
ABSTRACT
Inducible costimulatory molecule(ICOS)is a member of the CD28 family,which can be expressed on the tumor tissues and immune cells in the tumor microenvironment. ICOS enhances its anti-tumor activity through participating in CD4 + T and CD8 + T cell immune response and enhancing the secretion of cyto-kines on the activated T cells and NK cells. While the curative effect of cytotoxic T lymphocyte-associated anti-gen-4(CTLA-4)monoclonal antibody is relevant with CD4 + T cells expressing ICOS,which suggesting ICOS may become a novel anti-tumor therapeutic target in the future.
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Inducible costimulatory molecule (ICOS) is one of the costimulatory molecules CD28 superfamily and is upregulated on the surface of T cells following T cell activation.ICOS initiates costimulatory signals after binds with its ligand (ICOSL) and ICOS/ICOSL promote activation of T cells proliferation,differentiation and cytokine production.Clinical and laboratory researches documented that ICOS/ICOSL plays significant roles in various autoimmune diseases,similarly,it plays critical effects on the outcome and evolution of autoimmune uveitis (AIU) and Behcet disease.To further study the influence and mechanism of ICOS/ICOSL pathway on AIU is of helpful for finding out a new therapeutic approach of AIU.This paper reviewed the basic concept of ICOS,the relationship between ICOS/ICOSL pathway and effector cell,the outlook of ICOS/ICOSL in the treatment of AIU.