Objective To summarize the role of costimulatory molecules in inducing immune tolerance of organ transplantation. Methods Domestic and international publications online involving costimulatory molecules and immune tolerance in recent years were collected and reviewed. Results The relationship between costimulatory pathways and transplantation immunity has already been clarified in recent years. The main costimulatory molecules alreadly found mainly include B7-CD28/CTLA4, CD40-CD154, 4-1BB/4-1BBL, and ICOS-B7h, etc. Costimulatory pathways com-inhibition or combining with other immunosuppression methods could obtain stable and long lasting immune tolerance. Conclusions With the development of immunology and molecular biology, costimulatory pathways of T lymphocyte activation will be further interpreted. Other new costimulatory molecules will be discovered in the future, which will afford theory evidence for inducing immune tolerance.
ObjectiveTo evaluate the relationship between CT lesion changes in COVID-19 patients and different subgroups of T lymphocytes, providing reference information for assessing patient conditions, predicting outcomes, and evaluating treatment efficacy. MethodsClinical and imaging data of confirmed COVID-19 patients admitted to the Chongqing Public Health Medical Center from January 24 to March 15, 2020, were collected. Based on the absorption characteristics of lesions in CT images, patients were categorized into three groups: Group A (obviously continuously absorbed), Group B (stable-slow absorption), and Group C (progressive absorption). The relationship between CT changes and T lymphocyte subgroups was analyzed according to lesion absorption. ResultsA total of 47 patients were included, with 18 in Group A, 14 in Group B, and 15 in Group C. At different stages—admission, during treatment, and at the end of treatment—the levels of T lymphocytes were observed as follows: Group A>Group B>Group C. When lesions were absorbed, the average count of CD4+ T lymphocytes was (544.43 ± 163.34) cells/μl; when lesions showed little change or increased, CD4+ T lymphocyte levels decreased to varying degrees. During treatment, both Group A and Group B showed CD4+ T lymphocyte levels returning to above normal levels, with an average increase of 134 cells/μl in Group A, which was lower than that in Group B (192 cells/μl) and Group C (149 cells/μl). Finally, T lymphocyte levels reached normal in all groups, but Group A levels were higher than those in Groups B and C (P<0.05). Upon follow-up, the average CD4+ T lymphocyte count was (544.43 ± 163.34) cells/μl in 52 cases of lesion absorption, (339.06 ± 145.98) cells/μl in 31 cases of minimal change, and (230.50 ± 95.24) cells/μl in 16 cases of lesion progression, with statistically significant differences among the three groups (P<0.05). ConclusionsThe increase in lung lesions in patients indicates poor immune function, necessitating enhanced immune regulation. Conversely, if a decrease in T lymphocyte levels is detected during the course of the disease, attention should be given to the risk of lesion progression, and timely CT re-examinations should be conducted to monitor changes in lesions.
Objective To study the effect of anti-CD40L monoclonal antibody on the rejection of rat pancreatic islet xenografts and its mechanism. Methods The animal models of human-rat pancreatic islet xenografts were established and were treated with anti-CD40L monoclonal antibody. The levels of blood glucose of transplantation rats were measured and the survival of grafts and transplantation rats were observed after transplantation. The morphological changes of grafts were observed and the levels of cytokines (IL-2 and TNF-α) were quantified by ELISA. Results ①Level of blood glucose in all the rats with diabetes decreased to normal on day (2.3±0.2) after transplantation. The average level blood glucose of control group began to increase on day (8.1±0.6), while the treatment group began to increase on day (18.5±1.2) after transplantation, which was significantly postponed compared with control respectively (P＜0.01). ②Grafts of treatment group and control group survived for (22±8.2) and (10±2.1) days respectively. Survival of grafts in treatment group was significant longer than that in control group (P＜0.01). ③Survival of transplantation rats were (35±6.5) and (21±5.7) days in treatment group and control group respectively. The survival of transplantation rats in treatment group was significant longer than that in control group (P＜0.05). ④Levels of serum IL-2 and TNF-α in control group increased dramatically within (3.2±0.3) days and reached peak within (7.3±0.5) days after transplantation, which were significantly higher than those measured before transplantation (P＜0.01); While in treatment group, the levels of serum IL-2 and TNF-α began to increase on day (22.6±1.7) after transplantation, and reached peak on day (28.5±2.2), which was significantly postponed than those in control group (P＜0.01). Conclusion Anti-CD40L monoclonal antibody can inhibit the rejection of rat pancreatic islet xenografts and prolong the survival time of transplantation rats and grafts.
Objective To assess the effectiveness and safety of Chinese medicinal herbs for female immune-caused subfertility. Methods Databases included: MEDLINE (1966-2002.2), EMBASE (1984-2002.2), CBM (1978-2002.2) and Cochrane Controlled Trial Register, CCTR (Issue 1, 2002). Reference lists of trials were handsearched. Published randomized controlled trials (RCTs) whether blind or unblind, any languages and length of follow up were included. Treatments included Chinese medicinal herbs (single or compound). Controls were placebo and western medicine, or no intervention. Data were extracted independently by two reviewers and analyzed with Revman 4.2. Results Six RCTs were included, all of which were poor in methodological quality. Because of different therapies in the treatment and control groups, we did not perform meta-analysis. The No.1 anti-immune tablet was more effective than corticosteroid plus condom during intercourse both in the pregnancy rate (RR 3.75, 95%CI 1.61 to 8.75, P=0.002) and AsAb negative rate (RR 1.66, 95%CI 1.23 to 2.22, P=0.000 8). Bushen Xiezhuo Soup was more effective than antibiotic in the pregnancy rate (RR 2.97, 95%CI 1.60 to 5.50, P=0.000 6) and antisperm antibody (AsAb) negative rate (RR 2.33, 95%CI 1.54 to 3.54, Plt;0.000 1)。Zhenqi Zhuanyin Soup was as effective as IUI in pregnancy rate (RR 1.80, 95%CI 0.58 to 5.60, P＝0.31) but more effective than IUI in AsAb negative conversion rate (RR 9.61, 95%CI 3.22 to 28.67, Plt;0.000 1), Zhenqi Zhuanyin Soup combined with IUI was more effective than IUI in pregnancy rate (RR 3.60, 95%CI 1.32 to 9.85,P=0.01) and AsAb negative rate (RR 8.92, 95%CI 2.98 to 26.75, Plt;0.000 1). Conclusions Some Chinese medicinal herbs may work well in subfertility treatment. However, the evidence is too weak to draw a conclusion for there are deficiencies in strict randomization, blinding and follow-up.More strictly designed, randomized, double-blind, placebo-controlled trials are required.
Objective To summarize the role of the relationship between liver cancer and cellular immunological function, and the role of immune therapy in clinical application. Methods To analyze the relationship between liver cancer and cellular immunological function, and the present research situation of immune therapy for liver cancer in clinical application retrospectively via review the related domestic and foreign literatures. Results The cellular immune dysfunction existed in all liver cancer patients. The state of body’s cellular immunological function is closely related with the arising and development of liver cancer, and the lowness of cellular immunological function is an important factor of hepatocellular carcinoma hard to cure or recurrence and metastasis. Immune therapy plays an important role in the treatment of liver cancer by adjusting the body’s cellular immunological function. Conclusions Liver cancer is closely related with the body’s cellular immunological function. Immune therapy is expected to offer a new way for the treatment of liver cancer, which can also be used as an important auxiliary treatment way.
Objective To investigate the role and mechanism of heat shock protein 60 (HSP60) in induction of murine skin allograft tolerance. Methods At the age of 8-12 weeks, inbred female BALB/C (H-2d) mice (n=45) and CBA/N (H-2k)mice (n=15) were used as transplantation donors and C57BL/6 (H-2b) mice (n=60) as recipients. Recipients C57BL/6 (H-2b) mice were randomized into 4 groups (n=15). In group A, 1 cm × 1 cm Wolfe-Krause skin graft was excised from the back of BALB/C (H-2d) mice and hypoderma was scraped off aseptically, and then transplanted to the back of C57BL/6 (H-2b)mice. The method of skin transplantation in the other 3 groups was the same as to group A. In group B, C57BL/6 (H-2b) mice were treated with imcompleted Freund’s adjuvant (IFA) administration into the back 2 weeks before transplantation of BALB/C (H-2d) mice skin. In group C, C57BL/6 (H-2b) mice were administered HSP60 emulsified in IFA into the back 2 weeks before transplantation of BALB/C (H-2d) mice skin. In group D, C57BL/6 (H-2b) mice were treated with HSP60 emulsified in IFA into the back and followed by skin transplantation of CBA/N (H-2k) mice 2 weeks later. The delayed type hypersensitivity was determined 7 days after transplantation. One-way mixed lymphocyte reaction, the concentration of cytokines in the mixed lymphocyte reaction culture supernatant was determined 7 days and 25 days after transplantation. The survival time of skin allograft was observed. Results The survival time of skin allograft in groups A, B, C and D was 12.4 ± 0.5, 11.6 ± 0.8, 29.3 ± 2.6 and 27.6 ± 2.1 days, respectively. There was significant difference between groups A, B and groups C, D (P﹤0.05), while there was no significant difference between group A and group B as well as between group C and group D (P gt; 0.05). The counts of per minute impulse (cpm) of mixed lymphocyte reaction 7 days after transplantation in groups A, B, C and D was 12 836 ± 1 357, 11 876 ±1 265, 6 581 ± 573 and 6 843 ± 612, respectively. There was significant difference between groups A, B and group C and group D (P lt; 0.05), while there was no significant difference between group A and group B as well as between group C and group D (P gt; 0.05). The cpm of mixed lymphocyte reaction at 25 days after transplantation in group A, B, C and D was 13 286 ±1 498, 12 960 ± 1 376, 11 936 ± 1 265 and 12 374 ± 1269, respectively. There was no significant difference among 4 groups (P gt;0.05).The concentration of IL-10 in the mixed lymphocyte reaction culture supernatant in groups C, D were higher than that in groups A, B, and IL-2 and IFN-γ were lower than that in groups A, B 7 days after transplantation (P lt; 0.05), while there was no significant difference between group A and group B as well as between group C and group D (P gt; 0.05). There was no significant difference in cytokines among the 4 groups 25 days after transplantation (P gt; 0.05). The delayed type hypersensitivity in groups A, B, C and D 7 days after transplantation was 0.84 ± 0.09, 0.81 ± 0.07, 0.43 ± 0.05 and 0.46 ± 0.03 mm, respectively. There was significant differences between groups A, B and groups C, D (P lt; 0.05). While there was no significant difference between group A and group B as well as between group C and group D (P gt; 0.05). Conclusion HSP60 may play a role in induction and maintenance of murine skin allograft tolerance.
ObjectiveTo evaluate the effect of pre-infusion of allogeneic lymphoyctes treated with 5-FU on the rat liver graft. MethodsRat liver transplant models from Wistar to SD were established. Four groups were designed as following: control group: only liver transplantation without any other intervention; lymphocytes group: 1 ml of untreated lymphocytes (5×106/ml) from Wistar rats were preinfused into SD rats on day 7 and 4 separately before transplantation; lymphocytes with low concentration of 5-FU group: low concentration 5-FU (7.5 μg) treated lymphocytes were preinfused as above; lymphocytes with high concentration of 5-FU group: high concentration 5-FU (15 μg) treated lymphocytes were preinfused as above. Fas-L and CD8 expression were detected by immunohistochemistry method on day 7 after transplantation. ResultsThe integral opticaldensity (IOD) of Fas-L positive lymphocytes in the lobules of liver and portal areas were higher in lymphocytes with low concentration of 5-FU group than in the other groups （Plt;0.05）. There was no difference between lymphocyte group and lymphocytes with high concentration of 5-FU group （Pgt;0.05）. The IOD of CD8+ expression in lobules of liver was not different among all the three lymphocytes treated groups （Pgt;0.05）. But in portal areas, CD8+ expression was lower in the lymphocytes with low concentration of 5-FU group than in the other groups （Plt;0.05）. ConclusionPreinfusion of lymphocytes treated with low concentration 5-FU can induce graft immune tolerance, the probable mecanism of which is the increasing Fas-L expression in graft.
ObjectiveTo review the research progress of the roles of inflammation and immune response in the formation of pathological scar. MethodsThe recent literature concerning the formation mechanism of pathological scar was extensively consulted, inflammation and immune response involved in the formation of pathological scar was reviewed. ResultsThe formation of pathological scar is associated with inflammation and immune response, some inflammatory factors will promote the activation of immune cells, then induce immune cells releasing cytokines and aggravate inflammatory response. However, inflammation response also affects the level of immune response. So they work together to promote the formation of pathological scar by the immuno-inflammatory cells and media. ConclusionThe formation of pathological scar is not only related to inflammation response, but also involves in immune response. Moreover, immune response is the new progress in the study of pathological scar mechanism in recent years. Further research of immuno-inflammatory response will provide new ideas and corresponding basis for the prevention of pathological scar.
Objective To study the effect of allogeneic canine cord blood mesenchymal stem cells（cbMSC）transplantation on the distribution of CD4+T and CD8+T in infracted area of hearts. Methods Mononuclear cells of cord blood were isolated by density gradient centrifugation and amplified by adherent culture. 36 adult male dogs were divided into experimental group and control group. Animal models of acute myocardial infarction were established by ligating anterior descending coronary artery. The fourth generations of mesenchymal stem cells (MSC) were transplanted into infarcted area of hearts by left anterior descending coronary artery after 72h induced by 5-aza and transfected by LacZ. The survival of transplanted cells in hearts can be confirmed by βgal expression. CD4+T and CD8+T cells distributed in infarcted area were detected by immunohistochemical staining method. The ImagePlus 5.1 software was used to analyze the images. Results Cells transplanted into infarcted area could survive for a long time. 2, 4, 8 weeks after transplantation, the IOD of CD4+T in experimental group were 44.35±7.03, 19.29±4.11 and 20.27±3.51 respectively, and the CD4+T/CD8+T ratios were 0.63±0.12, 0.51±0.15 and 0.66±0.08. In control group, the IOD of CD4+T at 2, 4, 8 weeks after transplantation were 65.78±10.27, 28.02±2.59, 29.79±6.83, and the CD4+T/CD8+T ratios were 1.28±0.20, 1.34±0.09 and 1.50±0.16. The IOD of CD4+T and CD4+T/CD8+T ratio in experimental group were significantly lower than that in control group. In experimental group the IOD of CD8+T at 2, 4, 8 weeks after transplantation were 69.88±7.84 , 37.80±8.83 and 30.81±7.42, higher than that in control group which were 51.28±10.01, 20.87±4.50 and 19.91±2.87. Conclusion The preliminary results indicated that allogeneic cbMSC transplanted in infarcted area can escape from immune rejection, its mechanism may be associated withdecreasing the amount of CD4+T cells infiltrated in periphery of infarcted area and maintaining CD4+T/CD8+T ratios at a lower level.
Objective To investigate the clinical significance and expression of T helper cell secretory cytokines in esophageal squamous cell carcinoma tissues, which provide theoretical basis of reasonable and effective therapy for patients with esophageal carcinoma. Methods Fifty-six specimens of patients who underwent esophageal carcinoma resection were divided into two groups. Group A (n=28) included grade Ⅰand Ⅱ specimens of esophageal squamous cell carcinoma, group B (n=28) included grade Ⅲ and Ⅳ specimens of esophageal squamous cell carcinoma. Control group included 6 specimens of esophagitis. The expression of tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10) and transforming growth factor beta (TGF-β) in all specimens were detected. Results The positive expression of TNF-α,TGF-β and IL-10 in group A and group B were significantly higher than those in control group(Plt;0.01); the positive expression of TNF-α in group A was higher than that in group B, while the positive expression of TGF-β and IL-10 were lower than those in group B (Plt; 0.01). There was negative correlation between the positive expression of TNF-α and IL-10, TGF-β(Plt;0.01), and positive correlation between TGF-β and IL-10 (Plt; 0.01). The positive expression of TNF-α in patients of survival period in 3 years was lower than that exceed 3 years(F=36.25 ,Plt;0.01),while the positive expression of IL-10 and TGF-β in the patients of survival period in 3 years were higher than those exceed 3 years(F=29.29,26.69;Plt;0.01). Conclusion By the way of changing the level of cytokines secretion from T helper cells, esophageal squamous cell carcinoma tissues destroyed the balanced condition of patient’s immune system, which made esophageal carcinoma tissues escape the attack from the patient’s immune system and promote the invasion into surrounding tissues.