Objective To observe the effects of Thymosin α1 （Tα1） on acute rejection after liver transplantation and immune function of T cells. Methods Twenty recipients of liver transplantation due to primary hepatic carcinoma were divided into two groups: Tα1 group (n=10) and control group (n=10). Tα1 group received subcutaneous injection of Tα1 1.6 mg on the first day after liver transplantation and then twice a week for at least one month. Both Tα1 group and control group took same immunodepressants. Core biopsies were carried to compare the incidence rate of acute rejection between Tα1 group and control group. Peripheral T cellular immune function in these two groups was detected on 1 d before, 1 week, 2 weeks and 1 month after transplantation. Results There was not significant difference of incidence rate of acute rejection between Tα1 group and control group (Pgt;0.05). In the Tα1 group, CD4+, CD8+ lymphocyte cell counts and the CD4+/CD8+ ratio were significantly higher than those in the control group in 2 weeks and 1 month after transplantation (P＜0.05). Conclusion Use of Tα1 in recipients who also takes rountine immunosuppressants dose not increase the risk of occurring acute rejection after liver transplantation. Tα1 can significantly increase CD4+, CD8+ counts and CD4+/CD8+ ratio, which shows that Tα1 may improve recipients’ cellular immune function.
【Abstract】Objective This study was conducted to build experimental model of orthotopic liver transplantation in rat (ROLT) with the character of acute rejection; and to study the effect of cytotoxic T lymphocyte antigen 4 immunoglobulin G (CTLA4Ig) on prevention of rejection and the induction of immune tolerance of ROLT. Methods Build model of Wistar→SD ROLT(performed by the two cuff method) with character of acute rejection.Recipients were injected with CTLA4Ig 75 μg per ROLT into abdominal cavity after 2 days of operation. Contrast was made with no treatment group, the clinical characters, the liver function, the transplantated liver pathologic character and the concentrations of TNFα in serum were observed and measured on postoperative day 7. In treatment group, all above observation were done on postoperative month 4. Above all, determination of the effect of CTLA4Ig on preventing acute rejection and inducing tolerance in ROLT was observed.Results ①Recipients (no treatment group) died one by one within 6th～14th days; pathologic character of rejection in transplantation liver could be found; ② In treatment group, on postoperative day 7 and month 4, no clinical rejection character and no pathologic character of rejection in transplantation liver were found and serum concentration of cytokins related to TNFα found lower than that of contrast group(P＜0.05), and serum concentration of ALT、AST、TBIL、DBIL found lower too(P＜0.05); But serum concentration of TP and Alb was found higher than that of contrast group(P＜0.05). Conclusion ① CTLA4Ig treatment alone inhibits the rejection responce in ROLT. ② CTLA4Ig treatment can Prevent rejection and induce immune tolerance in ROLT model with characters of acute rejection; the serum concentration of cytokins related to TNFα can probably be used as evaluation standard of rejection in ROLT rejection.
To evaluate effect of recombinant human growth hormone (rhGH) on immunologic function in patients with gastrointestinal malignant tumor (GIMT). Before and 3 weeks after surgical treatment and administration of rhGH, the amount of T lymphocyte subset (T-LS) and soluble interleukin 2 receptor (sIL-2R) level were measured in 12 patients with GIMT, which were compared with 20 cases of normal control and 18 cases of GIMT treated by surgery alone. Result: ①In all GIMT patients, the serum CD＋3, CD＋4 level and the ratio of CD＋4/CD＋8 were lower than normal control and the sIL2R level was much higher; ②After operation, the serum CD＋3, CD＋4 level and the ratio of CD＋4/CD＋8 of all patients increased, the serum sIL2R level decreased; ③In patients recieved rhGH, the serum CD＋3, CD＋4 level and the ratio of CD＋4/CD＋8 were much more increased and the serum sIL-2R level much more decreased than those of surgery alone group. Conclusion: rhGH can enhance the immunologic function of patients with GIMT.
Objective To observe the level of vitamin D in patients with steroid resistant (SR) asthma, and investigate the effect of 1,25-(OH)2D3 on JNK/AP-1 and glucocorticoid receptor of T lymphocytes in SR asthmatics. Methods Sixty-two outpatients and inpatients with asthma with acute exacerbation between 2014 and 2015 were recruited in the study, including 26 cases of steroid sensitive (SS) asthmatics and 36 cases of SR asthmatics. Meanwhile 25 healthy volunteers were recruited as control. Clinical data were collected and peripheral venous blood was sampled for measuring the level of 25-(OH)D and separating the T lymphocytes. T lymphocytes were assigned to six groups, ie. a healthy control group (Group A), a SS asthmatics control group (Group B), a SR asthmatics control group (Group C), a SR asthmatics with JNK inhibitor (SP600125)+1,25-(OH)2D3 group (Group D), a SR asthmatics with JNK inhibitor (SP600125) group (Group E), and a SR asthmatics with 1,25-(OH)2D3 group (Group F). T lymphocytes were cultured for 48 hours. By the end of culture, the expression of phospho-JNK (p-JNK) and phospho-glucocorticoid receptor (p-GR) of T lymphocytes were detected by Western blot method, and the expression of c-Jun mRNA was detected by RT-PCR method. Results The level of 25-(OH) D was lower in Group B and Group C than Group A (P<0.05), and lower in Group C than Group B (P<0.05). The level of p-JNK was higher in Group B and Group C than Group A (P<0.05), higher in Group C than Group B (P<0.05), lower in Group E and Group F than Group C (P<0.05), lower in Group D than Group F (P<0.05). The level of p-GR was lower in Group C than Group A and Group B (P<0.05), higher in Group E and Group F than Group C (P<0.05), higher in Group D than Group F (P<0.05). The level of c-Jun mRNA was higher in Group B and Group C than Group A (P<0.05), higher in Group C than Group B (P<0.05), lower in Group E and Group F than Group C (P<0.05), and lower in Group D than Group F (P<0.05). The 25-(OH) D level was negatively correlated with the expression of p-JNK and c-Jun mRNA in Group C (r=–0.69, r=–0.65, P<0.05). However, there was a positive correlation between the 25-(OH) D level and p-GR (r=0.72, P<0.05). Conclusions There is a high prevalence of vitamin D deficiency or lack in SR asthmatics. 1,25-(OH)2D3 can promote the expression of p-GR by inhibiting the JNK/AP-1 signaling pathway of T lymphocytes in SR asthmatics, which may be one of the mechanisms of vitamin D to improve glucocorticoid resistance in SR asthmatics.
【摘要】 目的 研究人類免疫缺陷病毒(HIV)感染者和獲得性免疫缺陷綜合癥(AIDS)患者CD4+T淋巴細胞數變化(ΔCD4+T)和外周血淋巴細胞總數變化(ΔTLC)的相關性。探討用ΔTLC預測ΔCD4+T在監測HIV/AIDS患者疾病進展以及高效抗逆轉錄病毒治療(HAART)療效的價值。 方法 回顧性分析2005〖CD3/5〗2008年確診的91例HIV/AIDS患者的臨床資料。 結果 ΔTLC與ΔCD4+T呈直線正相關(r=0809,Plt;001),好于TLC與CD4+T的相關性(r=0712,Plt;001)。分別用ΔTLC 170、330、630、910個/μL細胞預測ΔCD4+T 50、100、200、300個/μL細胞時具有較好的預測價值,各項評價指標符合率基本達到90%以上,顯著高于相同時間下用TLC預測CD4+T計數的價值。 結論 應用ΔTLC預測ΔCD4+T,可比TLC更加直觀、準確的反映HIV感染者疾病進展和評價AIDS患者HAART的療效。【Abstract 】Objective To assess the utility of total lymphocyte count (TLC) changes (ΔTLC) in place of TLC to predict the development of HIV/AIDS. To investigate the monitoring value of ΔCD4+T on progress of HIV/AIDS and HAART which predicted by ΔTLC. Methods Clinical data of 91 patiens with HIV/AIDS diagnosed from 2005 to 2009 were retrospectively analyzed. Results A linear correlation was found between the value of ΔTLC and the value of CD4+T changes(ΔCD4+T)(r=0809,Plt;001),which was better than the correlation between TLC and CD4+T (r=0712,Plt;001).Using ΔTLC as 170,330,630,910 cells/μL,respectively for forecasting ΔCD4+T as 50,100,200,300 cells/μL,respectively,had a better predictive value with the area under ROC curve near to 09,significantly higher than using TLC for predicting CD4+T counts. Conclusion ΔTLC is more accurate than TLC to reflect the development of HIV/AIDS.
Objective To study the immunological tolerance induced by blocking the second signal of T cell with extrinsic cytotoxic T lymphocyteassociated antigen 4 immuno globlin(CTLA4-Ig). Methods Fifty-four BALB/C mice, inbred strains, were employed as recipients of bone allografts, using a model of heterotopic muscle pouch. The 54 mice were divided into 3 groups and18 for each group. The first group, in which the donor was C57BL/6 with intraperitoneal injection ofL6(as a control), was named AL group. The second group,also C57BL/6 with injection CTLA4-Ig, was named AC group. The third group,homologous BALB/C with injection of PBS buffer solution, was named AB group.The serum antibody, lymphocyte proliferation of the second stimulation by splenic cell and bone supernatant of donor, the analysis of lymphocyte subsets, a regraft experiment and histology were determined 2, 4 and 6 weeks after transplantation. The second transplantation was to regraft C57BL/6(BC group) and C3H(BHgroup) mice respectively after first 12 mice being transplantated with C57BL/6 and injected with CTLA4-Ig as to detect donor-specificity of immunological tolerance. Results Compared with AB group, AL group created more intensive immune rejection: CD4 T cell subsets(Plt;0.05), the serum antibody(Plt;0.05) and lymphocyteproliferation of the second stimulation by splenic cell and bone supernatant ofdonor (Plt;0.01 and 0.05) were significantly increased. However, the results of AC group showed that CTLA4-Ig significantly inhibited the immune rejection: CD4T cell subsets(Pgt;0.05), the serum antibody (Pgt;0.05), and lymphocyte proliferation of the second stimulation(Pgt;0.05) were similar to those of AB group. Histological observation of AC group showed that lymphocyte infiltration disappeared,cartilage and new bone formed, and bone marrow cavities emerged. A regraft experiment showed that CD4 T cell subsets (Plt;0.05) and lymphocyte proliferation of the second stimulation by splenic cell and bone supernatant of donor(Plt;0.05), BC group was significantly lower than those of BH group. So theimmunological tolerance induced by CTLA4-Ig was of donor-specificity. Conclusion The immunological tolerance induced by CTLA4-Ig was prolonged for 6 weeks. This study provides a brand-new path for bone transplantation, which can be helpful to other organ transplantation.
ObjectiveTo explore the functional heterogeneity of T lymphocytes in various organs after SARS-CoV-2 infection. Methods Using the public database GEO data (GSE171668, GSE159812, GSE159556, GSE167747) and the analysis method of single-cell technology, the functional differences of T lymphocytes in various organs of patients after infection with SARS-CoV-2 were analyzed. Results Through single-cell data extraction of 16 livers, 19 hearts,2 spleens, 6 brains, 58 lungs, 21 kidneys and 5 pancreases from SARS-CoV-2 infected patients, invasion genes were relatively highly expressed in T lymphocytes of the lung and pancreas. The lung had a special ability to express the interferon signaling pathway, while the expression of other organs was relatively low; at the same time, the T lymphocytes of the lung also highly expressed fatty acid binding sites. Conclusion After SARS-CoV-2 infection, compared with other organs, the lung has a special interferon-activated signaling pathway and fatty acid binding site.
ObjectiveTo investigate the method for generating anchor chemric T lymphocytes that can target tumor associated glycoprotein-72 (TAG72) antigen and analyze their repressive effects on proliferation of TAG72 positive hepatocarcinoma cells. MethodsFirstly, peripheral blood mononuclear cells (PBMCs) from healthy volunteers were isolated. And then, CD8+ T cells were isolated from PBMCs via magnetic activated cell sorting (MACS). These lymphocytes were transfected with recombinant vector, anti-TAG72-scFv-CD28-pcDNA3, through Lipofectamine2000 to gernerate anchor chimeric TAG72-specific CD8+ T cells. SMMC7721 (TAG72 positive) hepatocarcinoma cells were co-cultured with chimeric T lymphocytes and their cell cycles were analyzed by flow cytometry (FCM). ResultsAnchor chmeric T lymphcytes targetting TAG72 recognized TAG72 positive SMM7721 cells and repressive effects on their proliferation were observed by flow cytometry. ConclusionAnchor chmeric T lymphcytes targetting TAG72 on tumor surface can specifically recognize TAG72 positive hepatocarcinoma cells and may exert repressive effect on their proliferation.
Objective To observe the changes in the peripheral blood T lymphocyte subsets and the histomorphology of the transplanted tissues in the rabbits in the early stage after transplantation of the tissue engineered boneconstituted by the biologically-derived scaffold and to confirm the feasibility of the biologicallyderived materials as a scaffold in the bone tissue engineering. Methods Forty-eight healthy New Zealand rabbits (weight, 2.0-2.5 kg) with a 1-cm defect were equally and randomly divided into 4 groups: Groups A-D. The partial demineralized freeze-dried bone (PDFDB), the tissue engineered bone constructed by the osteoblasts derived from the lactant rabbit periosteum as a seeding cell, the xenogeneic cancellous bone undergoing the antigen self-digestion, partial demineralization and freeze-driedprocess as a scaffold, and the fresh xenogeneic allografting bone were respectively transplanted into the segmental defects of the rabbit radii in Groups A-D.To examine the effects of the 4 different materials, the flow cytometry was used to observe the changes in the T lymphocyte subsets in the rabbit peripheral blood at 1, 2, and 4 weeks after the operations and to examine the osteogenesis achieved by the 4 materials, the histological observations were also performed at 2, 4, 8, and 12 weeks after the operations. Results Two weeks after the tissue engineered bone transplantation in Group B, the osteoblasts and chondroblasts were found in the apertures of the scaffold, the new bone formation could be observed, the osteoclasts could be seen in the peripheral zone, and some of the netlike frameworks were destroyed and absorbed. Four weeks after the operation, the histological observation revealed that the osteocartilagionous callus turned into a woven bone. The peripheral blood T lymphocyte subsets of CD4+ and CD8+ were significantly greater in number 1-2 weeks after the operations and in Groups A and B than before the operations and in the other groups (.Plt;0.05)；4 weeks after the operations the T lymphocyte subset of CD4+ was only slightly greater in number than before the operations, but with no statistically significant difference (Pgt;0.05). In Group C, the increase of the T lymphocyte subsets of CD4+ and CD8+ was not significant after the operation (Pgt;0.05). The T lymphocyte subsets of CD4+ and CD8+ were significantly greater in number 1, 2 and 4 weeks after the operations and in Group D than before the operation and in the other groups (Plt;0.05). Conclusion The tissue engineered bone constructed by the partial demineralized freezedried bone as a scaffold does not cause a serious immunologic rejection in the early stage after the transplantation and does not affect its good ability to repair the bone defect. The biologicallyderived bone canbe used as a scaffold in the bone tissue engineering.
ObjectiveTo understand the interplay between tumor-associated macrophages (TAMs) and T lymphocytes, as well as the effect on the pathogenesis of hepatocellular carcinoma (HCC) again, so that providing new ideas and methods for the immunotherapy of HCC.MethodSearched the literatures about the interplay between TAMs and T lymphocytes in HCC to analyze and summarize the relationship between TAMs and T lymphocytes in HCC.ResultsWhile TAMs and T lymphocytes themselves regulate the process of tumorigenesis and development, they also had a mutual regulatory mechanism to further promote the development of HCC.ConclusionsThere is an interaction between TAMs and T lymphocytes, and this interaction forms a vicious circle to a large extent and promotes the development of HCC. Recognizing and making rational use of this interaction can provide new ideas and methods for the future immunotherapy of HCC.