ObjectiveTo investigate the levels of regulatory T cells (Treg) and FoxP3 gene in patients with gastric cancer before and after operation. MethodsTwenty patients with definite diagnosis of gastric cancer and 15 healthy volunteers were selected. The levels of Treg and T cell subsets in peripheral blood were determined by detecting of CD4 and CD25 with immunefluorescence stain and flow cytometry, the expressions of FoxP3 mRNA in these Treg were detected by RTPCR technique. The expression of FoxP3 protein in the gastric cancer tissue was measured by immunohistochemistry assay. ResultsThe percentage of Treg cells in total CD4+ T isolated from the patients with gastric cancer was higher than that of healthy volunteers 〔(19.39±5.58)% versus (9.91±3.23)%, Plt;0.01〕, and it markedly decreased after operation 〔（13.50±5.93）% versus (19.39±5.58)%, Plt;0.05〕. The FoxP3 mRNA expression in the patients with gastric cancer was also higher than that of healthy volunteers (0.86±0.03 versus 0.64±0.02, Plt;0.01), and decreased after operation (0.73±0.04 versus 0.86±0.03, Plt;0.05). The percentage of CD4+T cell in mononucleocytes of peripheral blood of patients with gastric cancer was significantly lower than that of healthy volunteers (Plt;0.01), but the difference was not significant between before and after operation. FoxP3 protein expressed in cytoplasm of 13 patients with gastric cancer, in which bly positive in 2 cases, middle positive in 6 cases, weakly positive in 5 cases. FoxP3 protein didn’t express in cytoplasm of 7 patients with gastric cancer. ConclusionsTreg may have a significant effect on the onset and development of gastric cancer through immunosuppressive effect. Tumor tissue is an important initiating agent on Treg proliferation.
Objective To explore the role of CD4+CD25+ Treg cells in chronic pulmonary infection caused by Pseudomonas aeruginosa(PA).Methods Sixty SD rats were randomly divided into a PA group and a control group(n=30 in each group).Chronic lung infection model was established by implantation of silicone tube precoated with PA into the main bronchus.Twenty-eight days later Treg cells in peripheral blood were measured by fluorescence-activated cell sorting（FACS）.Levels of IL-10 and TGF-β in serum were assayed by ELISA.The expression of Foxp3 mRNA in spleen was measured by RT-PCR.Pathological changes of lung tissue were studed by HE staining.Results Treg/CD4+ T cells in the PA group were significantly more than those in the control group[（19.79±6.45）% vs （5.15±0.47）%，Plt;0.05].The levels of IL-10 and TGF-β were (231.52±54.48)pg/mL and （121.05±7.98）pg/mL in the PA group respectively，which were significantly higher than those in the control group[（35.43±23.56）pg/mL and （36.02±8.94）pg/mL].The expression of Foxp3 mRNA in the PA group was significantly higher compared with the control group(0.80±0.044 vs 0.25±0.054，Plt;0.05）.HE staining revealed that PA caused a intensive inflammatory reaction with lymphocytes infiltration.Conclusion CD4+CD25+ Treg cell is up-regulated and plays an important role in chronic lung infection caused by Pseudomonas aeruginosa.
ObjectiveTo approach the role of CD4+CD25+ regulatory T cells in the maintenance of immunotolerance in mouse liver allograft. MethodsThe mouse orthotopic liver transplantation was performed. After the liver transplantation immunotolerance induction, antiCD25 monoclonal antibody (PC61) was injected into the recipients with a delayed timing to remove the CD4+CD25+ T cells. The percentage of CD4+CD25+ T cells and the expression of forkhead/winged helix transcription factor (Foxp3) in the recipients were examined. Furthermore, the survival time of the recipient was observed. ResultsC3H/HeJ recipients receiving DBA/2 hepatic allografts survived over 70 d as in the syngeneic liver transplantation (C3H/HeJ recipients receiving C3H/HeJ hepatic grafts). With various protocols of the delayed PC61 treatment, the CD4+CD25+ T cell was completely disappeared as observed. However, the removal of CD4+CD25+ regulatory T cells after the induction of transplantation immunotolerance did not affect the survival of hepatic allografts. ConclusionCD4+CD25+ regulatory T cells are not essential for the maintenance of spontaneous mouse liver transplantation immunotolerance.
Regulatory T cells (Treg) are critical for regulation of tolerance, control immune responses to self-antigens thereby preventing autoimmunity, and limiting responses to foreign antigens thereby minimizing T cell-mediated immunopathology. Recent data indicate that suppression of organ-specific autoimmunity is dependent on the antigen specificity of Treg. An emerging model of Treg action is that organ-specific Treg acquire suppressive activity through activation by dendritic cells expressing specific antigens. Thus, the efficacy of Treg-based therapy should be increased by using antigen-specific Treg rather than polyclonal Treg. It is necessary to identify relevant antigens and to expand antigen-specific Treg from polyclonal populations. Here, we discuss recent techniques for expansion of antigen-specific Treg, function and antigen specificity of Treg and the therapeutic potential of Treg in controlling autoimmune disease and inducing transplant tolerance.
Objective To compare the difference in the expressions of forkhead box protein 3 (FoxP3) and adenosine 2a receptor (A2aR) in gastric cancer tissues and its adjacent tissues, and to investigate the relationship between the elevated expression of FoxP3/A2aR and clinicopathological features in gastric cancer. Methods Gastric cancer tissues and their adjacent tissues from 52 patients with gastric cancer were collected, who underwent surgery in the Affiliated Hospital of Xuzhou Medical University from July 2015 to November 2016, immunohistochemical staining was used to detect the expressions of FoxP3 and A2aR. Results ① The high-expression rate of FoxP3 in gastric cancer tissues was 69.2% (36/52), which was higher than that of adjacent tissues (11.5%, 6/52), P<0.001. The high-expression rate of A2aR in gastric cancer tissues was 69.2% (36/52), which was higher than that of adjacent tissues (25.0%, 13/52),P<0.001. ② The expression of FoxP3 was positively correlated with the expression of A2aR in gastric cancer tissues (r=0.76, P<0.05). ③ In gastric cancer tissues, high-expressions of FoxP3 and A2aR were not related to gender, age, diameter of tumor, tumor location, degree of differentiation, gross type, and histological type (P>0.05), but both associated with TNM stage, T stage, number of lymph node metastasis, and distant metastasis (P<0.05), the high-expression rates of FoxP3 and A2aR in patients with stage Ⅲ+Ⅳ were higher than those of patients with stage Ⅰ+Ⅱ, the high-expression rates of FoxP3 and A2aR in patients with stage T3+T4 were higher than those of patients with stage T1+T2, the high-expression rates of FoxP3 and A2aR in patients with distant metastasis were higher than those of patients without distant metastasis, and the high-expression rates of FoxP3 and A2aR increased gradually with the increase in the number of lymph node metastasis. Conclusion There are high expressions of FoxP3 and A2aR in gastric cancer tissues, and both of them may play important role in promoting the occurrence and development of gastric cancer.
Objective To assess the effects of different immunosuppressive drugs on proliferation and function of regulatory T cells (Tregs). Methods We searched MEDLINE (1966 to November 2009), EMbase (from inception to September 2009), and The Cochrane Library (Issue 4, 2009) for clinical and basic research about the effects of various immunosuppressive drugs on Tregs. Data were extracted and methodological quality was assessed by two independent reviewers. Outcome measures for clinical research included blood Tregs levels, acute rejection episodes, and graft function. Outcome measures for basic research included percentage of Tregs proliferation, function, Tregs phenotype, and evidence for possible mechanisms. We analyzed data qualitatively. Results Forty-two studies, including 19 clinical trials and 23 basic studies, were included. The immunosuppressive drugs studied were calcineurin inhibitors (CNIs), Rapa, anti-metabolism drugs, IL-2 receptor-blocking antibodies, T-cell depleting antibodies, and co-stimulation blockade antibodies. Most of the studies were on Rapa and CNIs. Eight basic studies on Rapa and CNIs showed that Rapa could promote the proliferation and function of Tregs, while CNIs could not. Five clinical trials involving a total of 158 patients showed that patients taking Rapa had higher blood concentration of Tregs than those taking CNIs, but no differences were found in graft function (6-42-month follow-up). Conclusion There is substantial evidence that Rapa favors Tregs survival and function. However, the larger number of the blood Tregs in the patients treated with Rapa does not show any correlation with better graft function. Large-sample and high-quality clinical studies with longer follow-up are needed to thoroughly assess the efficacy of immunosuppressive drugs on Tregs and to reveal whether a relationship exists between Tregs and graft function.
ObjectiveTo investigate the proportion of peripheral blood CD4+CD25+ regulatory T cells (Tregs) in patients with pancreatic head carcinoma, the dynamic changes of these cells before and after pancreatoduodenectomy were also analyzed. MethodsThe proportions of peripheral blood CD4+CD25+ Tregs in patients with pancreatic head carcinoma and normal individuals were examined by using flow cytometric analysis. The CD4+/CD8+ ratio was also studied before and after operation. ResultsThe patients with pancreatic head carcinoma showed higher ratio of CD4+CD25+ and CD4+CD25high Tregs compared with normal control before operation (Plt;0.05). However, the percentage of these T cells reduced significantly after pancreatoduodenectomy, which was most obviously on the 3rd day after operation (Plt;0.01, Plt;0.05). After operation, CA199 level began to decrease, which was obvious on the fourteen day after operation. This tendency of CD4+CD25high Tregs changes was similar to that of CA199. The patients showed an decreased ratios of CD4+/CD8+ compared with normal controls, which further declined after operation, and reached the lowest point on the seventh day after operation (Plt;0.05). ConclusionsPancreatoduodenectomy may be helpful for the recovery of antitumor immunity. The perioperative period of patients with pancreatic head carcinoma may be a beneficial windowphase for immune intervention and Tregs may be served as target cells.
ObjectiveTo analyze the relation between regulatory T cell (Treg)/ helper T cell 17 (Th17) imbalance and the pathogenesis of acute pancreatitis (AP) and to explore the relation between Treg/Th17 cell imbalance and helper T cells 1, helper T cells 2 and cytokines in patients with AP, so as to provide a new therapeutic target for immunotherapy of AP. Methods From January to December 2020, 40 patients diagnosed with AP ( AP group) in The People’s Hospital of Xinjiang Uygur Autonomous Region and 40 healthy subjects who underwent physical examination (normal control group) during the same period in this hospital were selected as the research objects. Their peripheral bloods were collected and the proportion of Treg and Th17 cells was detected by flow cytometry. Plasma levels of interleukin-10 (IL-10) and interleukin-17 (IL-17) were detected. Results Compared with the normal control group, the proportions of Treg and Th17 cells increased before treatment in the AP group, the differences were statistically significant (t=5.78, P<0.001; t=5.82, P<0.001). The levels of IL-10 and IL-17 increased, the differences were statistically significant (t=7.14, P<0.001; t=35.22, P<0.001). After treatment, the AP group as compared with the normal control group, the proportions of Treg and Th17 cells increased but the differences were not statistically significant (t=1.87, P>0.05; t=0.29, P>0.05), the level of IL-10 increased and the difference was statistically significant (t=3.98, P<0.001), the level of IL-17 increased but the difference was not statistically significant (t=1.67, P>0.05). After treatment as compared with before treatment in the AP group, the proportions of Treg and Th17 cells decreased, the differences were statistically significant (t=3.07, P<0.01; t=4.99, P<0.001). The levels of IL-10 and IL-17 decreased, the differences were statistically significant (t=3.38, P<0.001; t=30.63, P<0.001). Conclusion In AP, Treg cells mediate immunosuppression and Th17 cells mediate inflammatory response, promoting the occurrence and development of inflammation in the disease. IL-10 and IL-17 may play an important role in regulating their differentiation and homeostasis.
ObjectiveThrough the analysis of quantitative and functional changes in peripheral blood CD4+ CD25+FOXP3+ regulatory T cells (Treg) of early HCC patients before and after operation, to discuss the operation effect on the immune function from the aspect of immune suppression. MethodsExtracted the lymphocytes of peripheral blood in HCC patients before and after operation (case group, n=15) and normal people (control group, n=5 cases), and analyze the number and function of Treg by flow cytometer after extracellular (CD4, CD25) and intracellular (FOXP3) staining. ResultsCD4+CD25+ T cells and CD25+FOXP3+ T cells in preoperative peripheral blood in case group were significantly higher than those in control group (12.43±2.57)% vs. (5.56±1.02)%, (5.14±1.4)% vs. (2.18±0.83)%, Plt;0.05). These two cells decreased at 1 week after operation. 〔(10.56±2.13)%, (4.28±1.08)%〕, but there was not statistically significant (Pgt;0.05), they decreased significantly at 2 weeks after operation 〔(7.30±0.89)%, (3.43±0.83)%， Plt;0.05〕. CD8+ T cells and CD4+CD25- T cells in preoperative peripheral blood in case group were significantly lower than those in control group 〔（23.42±1.80）% vs. （29.22±2.26）%， （36.14±1.12）% vs. （43.69±2.78）%， Plt;0.05〕， These two cells decreased significantly at 2 weeks after operation 〔（27.15±1.71）%， （40.30±2.00）%〕. The analysis on the Treg and AFP correlation found that they have low correlation (r=048, Plt;0.05 ). ConclusionsThe hepatectomy can improve the immune response of HCC patient. Treg may have a certain auxiliary significance in the diagnosis, treatment and prognosis of patients with hepatocellular carcinoma.