The aim of our study was to investigate and characterize regulatory T cells (Treg) in peripheral blood of patients with connective tissue diseases (Systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, poly- and dermatomyositis) as compared with blood from healthy controls. Treg cells were quantified and phenotypically characterized by flow cytometry while the expression level of Foxp3 mRNA was evaluated by real time PCR. A reduced percentage of peripheral blood Treg cells was found in patients than in controls, irrespective of the type of connective tissue disease. Treg cells, especially those expressing one of the phenotypical markers, seemed to differ not only between patients and healthy controls but also among types of diseases. Additionally, the presence of autoantibodies as well as disease activity appeared to be correlated with particular Treg cell populations, especially those expressing one of the examined phenotypical markers. Correlations with therapy suggested that glucocorticoids plus antimalarial or other immunosuppressor drugs diminished the percentage of Treg cells, especially of those with memory phenotype. These findings indicated dysregulations at the level of Treg cells and suggested an involvement of these cells in the pathology of connective tissue diseases. Moreover, our data are in agreement with the suggestion that Treg cells could be therapeutic targets for some autoimmune diseases.

Quantification and molecular characterization of regulatory T cells in connective tissue diseases

Sirolimus-based regimen promotes inhibitory costimulatory signal of HVEM/BTLA/CD160/LIGHT pathway in allo-renal recipients.

Purpose To investigate CD152 and PD-1 expression on T lymphocytes and the function of CD152- and PD-1–positive CD8 T cells in human acute liver allograft rejection. Materials and methods Sixty-three patients undergoing liver transplantation were enrolled in this study, including 26 cases with acute allograft rejection (Gr-AR) and 37 cases with stable allograft liver function (Gr-SF). The expression of CD152 and PD-1 on T lymphocytes and the expression of granzyme and perforin on CD152- and PD-1–positive CD8 T cells in peripheral blood were analyzed using flow cytometry. Results The peripheral CD4/CD8 ratio in Gr-AR was significantly lower than that in Gr-SF ( P P P Conclusions Down-regulation of the expression of negative costimulatory molecules such as CD152 and PD-1 on CD8 T cells may be associated with human acute liver allograft rejection.

CD152 and PD-1 Down-Regulation on CD8 T Cells Is Associated With Human Acute Liver Allograft Rejection

The calcineurin inhibitor–FK506–is a first‐line immunosuppressant that regulates T cell secretion of IL‐2 and other cytokines. However, the mechanism of its protective effect on target cells and its role on tumour recurrence and interaction with anti‐tumour immune checkpoint inhibitors, such as PD‐L1 blocking, are still unclear. Here, in a murine heart transplantation model, we observed the upregulation of programmed death‐ligand 1 (PD‐L1) expression by FK506 in both dendritic cells (DCs) and allografts. Blocking PD‐L1 during FK506 treatment increased IFN‐γ and TNF‐α expression, enhanced CD4+ and CD8+ T cell proliferation, and suppressed Treg differentiation. Moreover, PD‐L1 decreased T cell infiltration and induced T cell apoptosis in both the spleen and graft. PD‐L1 was not only required in FK506‐mediated immunosuppression but also upregulated by FK506. Treatment with SAFit2, a FKBP51 selective inhibitor, reduced the expression of PD‐L1 on DCs and the grafts and interfered with the immunosuppressive effect of FK506, suggesting that the mechanism depends on FK506‐binding protein (FKBP) 51 expression. Overall, our results add new insights into the role of FK506, not only on T cell cytokine secretion but also on co‐inhibitory molecular regulation and target cell immune privilege.

Novel immunosuppressive effect of FK506 by upregulation of PD‐L1 via FKBP51 in heart transplantation

Human complete NFAT1 deficiency causes a triad of joint contractures, osteochondromas, and B cell malignancy.

Aim We dynamically observed the expression of CD152 and PD-1 on T-cell surfaces in peripheral blood of liver allorecipients to explore the regulatory effect of FK506 on negative costimulatory molecules. Methods We evaluated 20 liver allorecipients, 19 end-stage liver disease patients, and 20 healthy volunteers for FK506 concentrations measured by an enzyme-multiplied immunoassay technique and flow cytometry to determine T-cell subsets as well as CD152 and PD-1 expression. Results After liver transplantation, the frequency of CD4+ T cells gradually decreased to significantly lower level than those in the disease controls (P Conclusion FK506 up-regulated the expression of CD152 and PD-1 on the T-cell surface inhibiting proliferation and activation of effector T cells, favoring the survival of allorecipients.

Regulatory Effect of FK506 on CD152 and PD-1 in the Liver Allorecipients

BACKGROUND With the change in people’s lifestyles, the incidence of colorectal cancer (CRC) is increasing. It is essential to study the efficacy of various treatment methods for CRC patients to prevent and treat CRC. AIM To investigate the efficacy of biofeedback therapy combined with Baduanjin in improving the quality of life and gastrointestinal hormone levels of patients with CRC. METHODS A total of 120 patients with CRC who were admitted to our hospital from June 2020 to June 2021 were included in the study. They were randomly divided into four groups (n = 30): the control group (group A), the biofeedback therapy intervention group (group B), the Baduanjin exercise intervention group (group C), and the combination group (group D). Patients in group A adopted the standard nursing mode and necessary health education. Patients in group B were treated with biofeedback therapy based on routine nursing care. Patients in group C were given Baduanjin intervention for 12 wk based on conventional drug treatment and care. Patients in group D were treated with biofeedback therapy and Baduanjin exercise. In this study, patients’ quality of life, gastrointestinal hormone levels, and clinical efficacy in the four groups were observed at baseline and 12 wk after intervention. Meanwhile, the correlation between gastrointestinal hormone levels and various functional areas of quality of life was analyzed. By comparing the observed indicators of patients in the four groups, the efficacy of biofeedback therapy combined with Baduanjin in improving the quality of life and gastrointestinal hormone levels of patients with CRC was explored. RESULTS At baseline, there were no significant differences in quality of life, gastrointestinal hormone levels, or clinical efficacy among the four groups (P > 0.05). Twelve weeks after the intervention, the combination group’s quality of life, gastrointestinal hormone levels, and clinical effectiveness were better than those of the three other groups. CONCLUSION On the basis of routine nursing care, patients with CRC combined with biofeedback therapy and Baduanjin exercise can improve the quality of life of patients with CRC and the efficacy of gastrointestinal hormone levels.

Biofeedback therapy combined with Baduanjin on quality of life and gastrointestinal hormone level in patients with colorectal cancer

AIM: To investigate the expression of GITR on T cells and the expression of Foxp3+CD4+CD25+ regulatory T cells in the peripheral blood of patients with SLE. METHODS: The expression of GITR and Foxp3+CD4+CD25+ regulatory T cells in the peripheral blood was determined by flow cytometry (FCM). RESULTS: Compared with health control, the expression of Foxp3+CD4+CD25+ regulatory T cells in peripheral blood from SLE patients was lower (P0.05), but there is no difference in the expression of Foxp3+CD4+CD25+ regulatory T cells between active and inactive SLE patients (P0.05). GITR expression on both CD3+CD4+T cells and CD3+CD8+T cells of SLE patients increased significantly (P0.05). With the development of SLE activity, GITR expression didn’t change significantly on both CD3+CD4+T cells (P0.05) and CD3+CD8+T cells (P0.05). CONCLUSION: The expression abnormality of both Foxp3+CD4+CD25+ regulatory cells and GITR may play important role in the imbalance of immune homeostasis in SLE.

Hong-gang Wei

Papers

Regulatory Effect of FK506 on CD152 and PD-1 in the Liver Allorecipients

Biofeedback therapy combined with Baduanjin on quality of life and gastrointestinal hormone level in patients with colorectal cancer

[Analysis of Foxp3+ CD4+ CD25+ regulatory cells in peripheral blood of patients with SLE].