Objective To investigate the effects of nuclear factor kappa B decoy oligodeoxynucleotides ( NF-κB decoy ODN) transfection on biological characteristics of mature dendritic cells ( mDCs) in mice. Methods Immature DCs were harvested from Balb / c mice bone marrow, followed by the incubation with antigen OVA and LPS, and mature DCs were evaluated by the expressions of CD11c and MHC-Ⅱ detected by FACS. Mature DCs were transfected with NF-κB decoy ODN and the changes of NF-κB activity after the transfection were detected by EMSA. The expressions of the costimulatory molecules( CD40,CD80 and CD86) on DCs were detected by FACS and the proliferation of T cells was tested by mixed lymphocyte reaction( MLR) . Results The mature DCs were cultured successfully. The NF-κB activity of NF-κB decoy ODN transfected DCs was decreased significantly( P lt; 0. 05) . There was no difference in the expressions of CD40 and CD80, but the expression of CD86 was decreased significantly in NF-κB decoy ODN transfection group( P lt; 0. 05) . MLR test showed that the proliferation of T lymphocyte cells was inhibited by NF-κB decoy ODN transfected DCs, but was stimulated bly by the DCs of other groups. Conclusions Mature DCs transfected with NF-κB decoy ODN could inhibit the proliferation and activation of antigenspecical T cells, which was probably related to the down-regulation of CD86 on DCs. This modified DCs might be a promising vaccine for the treatment of asthma in the future.
Objective To investigate the effect of pre-infusion with allogeneic lymphocytes treated by 5-FU on inducting immune tolerance of liver transplantation in rats. Methods Wistar and SD rats were used as liver transplantation donors and recipients, respectively. They were divided into 4 groups as following: control group: liver was transplanted from Wistar to SD rats without any other treatment; lymphocytes group: recipient was pre-infused lymphocytes （5×106 cell/ml, 1 ml） from Wistar rat 7 d and 4 d separately before transplantation; low concentration of 5-FU with lymphocytes group: lymphocytes were treated by 5-FU (7.5 μg) before pre-infusion; high concentration of 5-FU with lymphocytes group: lymphocytes were treated by 5-FU (15 μg) before pre-infusion. Pathological changes were observed on day 7 after liver transplantation. Results Acute slight rejection was observed in low concentration of 5-FU with lymphocytes group: liver cell cords were well-arranged basically, hepatic lobules structures could be observed, a few inflammatory cells infiltrated around central veins, and a few lymphocytes infiltrated around portal area. Acute severe rejection was observed in control group, and acute moderate rejection was observed in high concentration of 5-FU with lymphocytes group and lymphocytes group. Conclusion Pre-infusion of lymphocytes treated with low level 5-FU can induce immune tolerance better in recipients after liver transplantation.
OBJECTIVE: To investigate the influence of tissue engineered tendon on subgroup of T lymphocytes and its receptor in Roman chickens. METHODS: The flexor digitorum profundus of the third toes of right feet in 75 Roman chickens were resected and made 2.5 cm defects as experimental model. They were randomly divided into five groups according to five repair methods: no operation (group A), autograft (group B), fresh allograft (group C), polymer combined with allogenous tendon cells (group D), derived tendon materials combined with allogenous tendon cells (group E). The proliferation and transformation of lymphocytes and contribution of CD4+, CD8+, CD28 and T cell receptor (TCR) were detected to study the immune response. RESULTS: The CD4+, CD8+ and TCR of group D and E were increased slightly than that of group B after 7 days, while after 14 days, those data decreased gradually and no significant difference between tissue engineered tendon and autografts (P gt; 0.05), and there was significant difference between fresh allograft and tissue engineered tendon (P lt; 0.05). Lymphocytes transformation induced by conA also showed no significant difference between tissue engineered tendon and autografts (P gt; 0.05). CONCLUSION: Tendon cells are hypoantigen cells, there are less secretion of soluble antigen or antigen chips dropped out from cells. Tissue engineered tendon has excellent biocompatibility.
Objective To explore the association between plasma IgG and acute exacerbation (AE) or death risk in patients with chronic obstructive pulmonary disease (COPD). Methods A total of 262 COPD patients treated in our hospital from February 2018 to February 2020 were recruited in our study. All patients were divided into AE≥2 group and AE≤1 group according to AE frequency during follow-up of 1 year. Basic data and laboratory data such as IgG, IgA and IgM of two groups were comparatively analyzed. Univariate analysis and COX regression were performed to analyze the related factors of frequency of AE≥2 times in 1 year. Depicting restricted cubic spline was performed to analyze the relation between IgG and AE by R software. All patients were also divided into high IgG group, low IgG group, high IgA group and low IgA group based on median of patients’ baseline plasma IgG and IgA level, depicting survival curve by Kaplan-Meier to analyse differences between the groups with different IgG or IgA level in the risk of AE and death respectively. ResultsFinally, there were 14 patients lost to follow-up and 248 cases were included (AE≤1 group contained 154 cases, AE≥2 group contained 94 cases) until February 28, 2021. Age and COPD Assessment Test (CAT) scores in the AE≥2 group were higher than those in the AE≤1 group; Albumin, IgG and IgA level in the AE≥2 group were lower than those in the AE≤1 group; Neutrophil to lymphocyte ratio (NLR) in the AE≥2 group was higher than that in the AE≤1 group (all P<0.05). There were 99 and 114 cases of AE in the high IgG and low IgG groups respectively within 1 year. Kaplan Meier survival analysis showed that risk of AE in the high IgG group and high IgA group were lower than that in the low IgG group and the low IgA group (log rank χ2=23.791, 67.153, both P=0.000). Risk of death in the high IgG group was lower than that in the low IgG group (log rank χ2=6.214, P=0.013), there was no statistically difference in the risk of death in the high IgA group compared to the low IgA group (log rank χ2=2.400, P=0.121). Multivariate Cox regression analysis showed that CAT score (HR=1.096, P=0.001) and NLR (HR=2.061, P=0.000) were independent risk factors of frequency of AE≥2 times in 1 year for COPD patients, albumin (HR=0.921, P=0.006) and IgG (HR=0.572, P=0.000）were the independent protective factors. Restricted cubic spline analysis showed that combining the COX regression model, after adjusting for IgA, albumin, NLR and other variables, there was non-linear relationship between IgG level and AE (P=0.000).Conclusion Plasma IgG level is related to AE in COPD patients, and may become a reliable predictor of acute exacerbation risk in the future.
Objective To explore the research status and development tendency of relation between indoleamine 2，3-dioxygenase （IDO） and immune escape of gastric cancer. Methods The related literatures about IDO， immune escape of gastric cancer， and their the relationship at domestic and international in recent ten years were collected and reviewed. Results Gastric cancers induced that dendritic cells expressed IDO by the CD4＋ CD8＋ regulatory T cells， which made the microenviroment tryptophan starvation， thus inhibited T cell proliferation. While tryptophan metabolites existed T cell cytotoxicity that inhibited T cell proliferation. IDO-specific inhibitor 1-MT combinated with chemotherapy drugs in the treatment for gastric cancer was a synergistic effect. Conclusions IDO as an immune modulating enzymes may play a key role in the process of immune tolerance that induced by gastric body. IDO may become a new target for inhibition of gastric malignancy formation and enhance the effectiveness of tumor immune treatment.
Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology by regulating the interaction between immune cells and cancer cells and promoting the disinhibition of the immune system, thus targeting various types of malignant tumors. However, the regulation of the immune system can also trigger related adverse reactions. Currently, there are no specific clinical guidelines for the treatment of these adverse reactions. Treatment decisions largely depend on clinical judgment and experience.The pathogenesis of ICI-related ocular adverse events is not fully understood at present. Further research on the specific mechanisms of action can provide new insights into the early diagnosis and treatment of ICI-related ocular adverse events.
Objective To observe the effect of transfer of immature mouse myeloid dendritic cells （DC） generated with low-dose granulocyte-macrophage colony-stimulating factor （GM-CSF） on cardiac allograft survival. Methods Mouse DC were generated with standard doses or low doses GM-CSF from bone marrow cells, the phenotype and functional properties of these DC were compared through fluorescence-activated cell sorting（FACS） analysis and mixed lymphocyte reaction（MLR）, 1. 0 × 106 DC generated with low doses GM-CSF were administered to the recipients 7 days before transplantation, and the cardiac allograft survival were observed. Results In contrast to DC generated with standard doses, DC generated with low doses were phenotypically immature DC （CD11c＋, CD80- , CD86- , MHCⅡlow）, and induced allogeneic T cell unresponsiveness, and administration of these DC to recipients prolonged cardiac allograft survival from 6.3±1.2 days to 14.3±1.9 days. Conclusions DC generated from mouse bone marrow progenitors in low doses of GM-CSF are phenotypically and functionally immature, and prolong cardiac allograft survival when they are administered 7 clays before transplantation.
Objective To analyze the clinical features of immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer. Methods The case data of patients with CIP admitted to Zhongshan Hospital of Fudan University from January 2017 to December 2020 were retrospectively collected, and the basic data, clinical manifestations, imaging data, laboratory examination results, treatment and prognosis of the patients were analyzed. Results The ratio of male to female was 18:1, and the median age was 65 years (from 41 to 74 years). Fourteen patients received a programmed death protein-1 (PD-1) inhibitor and five patients received a programmed death protein-ligand-1 (PD-L1) inhibitor. The median time to CIP was 3.5 months. The respiratory symptoms of 15 patients were dyspnea in 11 cases, cough in 9 cases, chest tightness in 8 cases, fever in 4 cases, expectoration in 4 cases and hemoptysis in 2 cases. Chest CT findings mainly showed interstitial pneumonia, including 8 cases of implicit organizational pneumonia (COP), 7 cases of non-specific interstitial pneumonia (NSIP), 2 cases of acute interstitial pneumonia, and 2 cases of allergic pneumonia. C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase were higher in CIP than before, and the difference was statistically significant. Follow-up observation was performed in 3 patients alone, 14 patients were treated with glucocorticoid alone, 2 patients were treated with immunosuppressant therapy, 19 patients had stable or more absorption of pneumonia lesions, and 5 patients had restarted immunotherapy. There were no deaths from CIP. Conclusions CIP mainly occurs in men, with slow onset, lack of specificity in clinical manifestations, and increased inflammatory indicators. Imaging findings are mainly NSIP and COP changes. Early identification, diagnosis and rational application of glucocorticoid therapy have good effects.
Objective To introduce the research progress in the immune of composite tissue allotransplantation. Methods The related articles were reviewed to summarize the immune characteristics, experimental developments, and cl inical experiences of composite tissue allotransplantation. Results Composite allogeneic tissue is on the body surface, including the composition of the complex with high antigenicity. There are a lot of differences in the immune responsesbetween composite tissue allotransplantation and organ transplantation, such as immunosuppressant protocol, rejectiondiagnosis, and chronic rejection. Conclusion In the next study, it is urgently needed to learn these experiences and toestabl ish the special standard of composite tissue allotransplantation in induction of immune tolerance, local medication, and rejection diagnosis.
Objective To investigate the rationale of immune privilege of testicular sertoli cell. Methods Testicular sertoli cell was prepared by digested collagenase, trypsin, and Dnase. In vitro, the sertoli cells were culture together with active lymphocytes to observe the effect on killing lymphocytes. SABC was used for labeling the Fas ligand on testicular sertoli cell.Results In vitro, sertoli cell can kill the active lymphocytes, and testicular sertoli cell expresses the Fas ligand. Conclusion Fas ligand expressing on the testicular sertoli cell may be the cause of immune privilege of testicular.