Objective To investigate the expression of T cell receptor (TCR) Vβ8.3 gene on CD4+ T lymphocytes in the rats with experimental autoimmune uveoretinitis (EAU). Methods Eighteen Lewis rats were divided into EAU, complete Freund′s adjuvant, and the control group. Inter photoreceptor retinoid-binding protein (IRBP) R16 peptide was synthesized using Fmoc procedure for induction of EAU. Magnetic absorption cell sorting (MACS) me thod was used to isolate the CD4+T lymphocytes from the spleen of the rats. Flow cytometry was used to monitor the efficiency of isolation. The expression of TCR Vβ8.3 gene segment on CD4+T lymphocytes was determined by fluorescent quantitative polymerase chain reaction. Results EAU was successfully induced in the Lewis rats immunized with IRBP R16 peptide. The proportion of CD4+T lymphocytes isolated by means of MACS was statistically higher than that before isolation (P＜0.001). The expression of TCR Vβ8.3 gene segment on CD4+ T lymphocytes in EAU rats was significantly higher than that in the control (P＜0.05). Conclusions There is a predominant usage of antigen-specific TCR Vβ 8.3 gene in EAU rats induced by IR BP R16 peptide, which may serve as a target for immunotherapy of EAU. (Chin J Ocul Fundus Dis，2004，20：165-167)
Objective To investigate the role of T cell factor-4 (TCF-4) in the carcinogenesis of colorectal cancer. Methods Relevant references about TCF-4 and the carcinogenesis of colorectal cancer, which were published recently domestic and abroad, were collected and reviewed. Results For TCF-4 gene, multiple isoforms are generated by way of alternative splicing, which encode different proteins. TCF-4 protein is sequence-specific DNA binding protein and is incapable of activating or repressing transcription independently, but it can interact with distinct partners to lead to different effects through multiple domains. Conclusion TCF-4 might be viewed as nuclear vehicles targeting other auxiliary proteins to a specific set of promoters and functions as molecular switch during the carcinogenesis of colorectal cancer.
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.
ObjectiveTo compare the clinical recovery and immune response between laparoscopic-assisted and open D2 gastrectomy for advanced gastric cancer. MethodsThe clinical data of 53 patients with advanced gastric cancer from January 2012 to October 2013 were studied prospectively. According to random number table, patients were randomly divided into laparoscopic-assisted group(LA group, n=27) and open operation group(OO group, n=26). Operative time, blood loss, time to passage of flatus, time to resume soft diet, after bed time, postoperative hospital stay, and number of retrieved lymph nodes were compared respectively between the two groups. The changes in CD3, CD4+, CD8+, IgG, IgA, IgM, and CRP were examined respectively by using flow cytometry and immunoturbidimetric assays on the preoperative day 1, and on the postoperative day 1 and 7. ResultsThe operative time was longer significantly in LA group than that in OO group(P < 0.05). The mean blood loss, the first flatus time, after bed time, and postoperative hospital stay in the two groups were all different statistically(P < 0.05), and all were better in LA group. However, the mean number of retrieved lymph nodes and the time to resume soft diet were not significantly different in the two groups(P > 0.05). On the day 1 and 7 after operation, the CD3, CD4+, and CD8+ significantly decreased as compared with those preoperatively in two groups(P < 0.01, P < 0.05). On the day 1 after operation, the levels of IgG, IgA, and IgM significantly decreased as compared with those preoperatively in two groups(P < 0.05). Those immunoglobulin in LA group recovered to close to the level before surgery, but in OO group sustained lower level(P < 0.05). On the day 1 and 7 after operation, CRP level significantly increased as compared with those preoperatively in two groups(P < 0.01, P < 0.05). Those changes of above index were not significantly different between the LA group and OO group on the day 1 after operation(P > 0.05). All index recovered gradually in the two groups on the day 7 after operation and were better in LA group(P < 0.05, except IgA). ConclusionLaparoscopic radical gastrectomy for advanced gastric cancer resulted in a quicker clinical recovery and a lesser depression to the perioperative cellular and humoral immune function.
ObjectiveTo investigate the expression of CD4+CD25highCD127lowTreg (Treg) and related cytokines in peripheral blood of COPD patients with pulmonary hypertension and explore its clinical significance. MethodsPeripheral blood lymphocytes and serum were collected from 65 COPD patients with chronic pulmonary hypertension (the CPH group) and 20 COPD patients with normal pulmonary artery pressure (the control group). Flow cytometry was used to detect the Treg/CD4+ T cells and calculate its ratio, enzyme-linked immunosorbent assay was used to detect the serum contents of interleukin (IL)-6,IL-10 and tumor necrosis factor α (TNF-α). ResultsTreg can be detected in the peripheral blood of patients of COPD with or without PH, however, the Treg ratio in the CPH group was significantly lower than that in the control group [(7.41±1.12)% vs. (9.04±2.11)%, P<0.05]. Compared with the control group, the IL-10 level was significantly lower [(4.47±0.88)pg/mL vs. (5.18±0.26)pg/mL], while IL-6and TNF-α contents were significantly higher in the CPH group [(7.49±0.95)pg/mL vs. (6.76±0.35)pg/mL, (28.61±9.16)pg/mL vs. (19.64±4.85)pg/mL, P<0.05]. There was a positive correlation between Treg ratio and serum IL-10 level (r=0.41, P<0.05), and negative correlation between Treg ratio and TNF-α or IL-6 contents (r=0.45 or 0.37,P<0.05). The Treg ratio of the patients with severe pulmonary hypertension was lower than that in the patients with mild pulmonary hypertension [(7.42±1.03)% vs. (10.47±2.55)%,P<0.05). ConclusionsContents of Treg and IL-10 decrease while IL-6 and TNF-α increase in peripheral blood of COPD patients with pulmonary hypertension. It suggests that Treg cells and related cytokines may involve in the pathogenesis and progression of CPH. Treg may becomea potential biological prognosis indicator and treatment target of CPH in the future.
ObjectiveTo improve clinicians' understanding of severe cytokine release syndrome (CRS) through reporting the clinical manifestation, diagnosis, treatment, and prognosis of CRS after chimeric antigen receptor T (CAR-T) cell therapy in a patient with solid tumor. Methods A patient with ovarian cancer who suffered severe CRS after CAR-T cell therapy in the Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University was reviewed. Relevant studies were searched for literature review. Results The patient, a 55-year-old woman, was diagnosed with ovarian cancer in early 2016 and continued to progress despite multiple lines of treatment, so she received CAR-T cell therapy on September 16, 2022. The patient developed a fever 2 days after infusion, and developed dyspnea and shortness of breath with oxygen desaturation 2 days later. Her condition kept deteriorating with respiratory distress and severe hypoxia 6 days after infusion, and the level of interleukin-6 and interferon-gamma continued to be elevated. Chest CT showed pleural effusion and massive exudation of both lungs. Considered to have acute respiratory distress syndrome (ARDS) due to severe CRS, she was transferred to the intensive care unit (ICU). The patient was treated with tocilizumab, high-dose intravenous glucocorticoid pulses, mechanical ventilation, and sivelestat sodium for ARDS. Her symptoms were gradually relieved, and the results of laboratory tests were gradually stabilized. The patient was extubated 6 days after ICU admission and discharged from ICU a week later. Six patients were screened out with ARDS or acute respiratory failure caused by CRS after CAR-T cell therapy, whose treatments were mainly anticytokine agents combined with high-flow oxygen therapy or invasive mechanical ventilation. One of them died. ConclusionsClinicians should be alert to severe CRS during the administration of CAR-T cell. Rapid interruption of the inflammation development is the key to all treatments. If respiratory and/or circulatory dysfunction occurs, patients should be transferred to ICU in time for organ support therapy.
目的 探讨“5.12”地震后北川羌族人群中类风湿关节炎（RA）患者外周血 T细胞亚群的表达情况并分析创伤后应激障碍（PTSD）对RA患者细胞免疫之间的影响。 方法 2009年3月－2010年3月，对98例北川羌族RA患者、112例健康对照，以及同期绵阳郊区84例RA患者、120例健康对照进行分析。用流式细胞仪分别检测CD3+、CD3+CD4+、CD3+ CD8+ T淋巴细胞数及CD4/+CD8+比值， RA疾病活动性采用DAS28测定，应用美国精神障碍诊断与统计手册第4版（DSM-Ⅳ）诊断标准调查RA人群中的PTSD患者，应用PTSD检查表平时版（PCL-C）检查对PTSD患者进行分析。 结果 北川羌族与绵阳郊区RA活动组患者（分别为58例、39例）与健康对照组比较，CD8+ T淋巴细胞数降低，CD+4/CD8+比值增高，差异有统计学意义（P＜0.05）；北川羌族RA活动组与绵阳郊区RA活动组比较，CD3+ T淋巴细胞数降低，差异有统计学意义（P＜0.05）。北川RA患者中PTSD者（38例）与非PTSD者（60例）比较，PTSD组CD3+ T淋巴细胞数和CD4+/CD+8比值均明显低于PTSD组，差异有统计学意义（P＜0.05）；PCL-C对北川RA患者中PTSD的测定发现，PCL高分组CD3+ T淋巴细胞数显著低于PCL低分组（P＜0.05）。 结论 “5.12”地震后一部分RA患者出现T细胞免疫功能异常，且免疫功能异常与PTSD有关，对合并有PTSD的进行RA患者早期心理干预及药物治疗，改善患者生存质量。
ObjectiveTo investigate the relationship between peripheral T cell apoptosis and specific immune tolerance induced by T cell vaccination（TCV）. MethodsT cell vaccinations were made from the spleen cells of SD rats, which were induced by ConA and were challenged with the spleen cells of Wistar rats. Normal SD rats were vaccinated intraperitoneally with TCV (experimental group) or RPMI 1640 culture buffer (control group) respectively .Oneway mixed lymphocyte reaction (MLR) were performed,the apoptosis of peripheral T cell were assayed using flow cytometric analysis before and after vaccination.ResultsIn experimental group, the result of MLR showed that the response captivity of SD rat spleen cells were suppressed significantly after vaccination in comparison with prevaccination (Plt;0.01) and the percentage of peripheral T cell apoptosis was increased significantly after vaccination compared with prevaccination (Plt;0.01); In control group, there was no significant difference between prevaccination and postvaccination about MLR and peripheral T cell apoptosis. ConclusionT cell vaccination is capable of inducing Agspecific immune tolerance, the T cell apoptosis of peripheral blood induced by T cell vaccination may result in the depletion of Agspecific reactive T cells, which is vital in inducing specific immune tolerance.