Abstract:SUMMARY
CD4+ (helper/inducer) T lymphocyte subsets were studied in the peripheral blood from patients with mixed connective tissue disease (MCTD) by double‐labelling immunofluorescence. The proportion of CD4+CD45RA+ cells was higher (P < 0·01) when compared with controls, whereas CD4+CD29+ cells were markedly diminished (P < 0·001). CD4+CD29+ cells were lower than in patients with progressive systemic sclerosis who were studied in parallel. Upon stimulation with phytohaemagglutinin, CD4+ cells from MCTD patien… Show more
“…In the early immune response, cross-talk between T cells and antigen-presenting cells initiate the production of certain patterns of cytokines, which was dictated by the type of invaded antigen, and orchestrates the subsequent development of CD4+T cell subsets [13]. Each subset plays a unique role in the elimination of invaded antigen, and dysregulated subset differentiation has long been associated with disease [29,30]. In the present study we demonstrated a Th17/Treg-related cytokine profile in patients with PBC with significant increases in IL-1b, IL-6 and IL-23, which were theoretically prone to Th17 differentiations and averse to Treg differentiation.…”
SummaryPrimary biliary cirrhosis (PBC) is an organ-specific autoimmune liver disease characterized by progressive loss of intrahepatic small bile ducts. Cellular immune mechanisms involving T cell reaction are thought to be involved significantly in the pathogenesis of PBC. Recent studies have independently revealed enhanced T helper type 17 (Th17) response and weakened T regulatory cell (Treg) response in some autoimmune diseases, indicating a role of Th17/Treg imbalance in the pathogenesis of autoimmunity. This prompted us to investigate whether the Th17/Treg balance was broken in the peripheral blood of patients with PBC and, if it was, what cytokine circumstances might contribute to this imbalance. The expression of 11 Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 36 patients with PBC, 28 patients with chronic hepatitis B and 28 healthy controls were measured by real-time quantitativepolymerase chain reaction and enzyme-linked immunosorbent assay respectively. Peripheral Th17 and Treg cells were analysed by flow cytometry. Th17-related cytokines were increased significantly in patients with PBC. Consistent with the cytokine profile, the Th17 cell population and retinoidrelated orphan receptor gt expression were increased markedly. In contrast, the Treg cell population and forkhead box P3 expression were decreased dramatically in the peripheral blood of patients with PBC. Our study revealed that the Th17/Treg imbalance, both cytokine profile and cell numbers, exists in patients with PBC, suggesting its potential role in the breakdown of immune self-tolerance in PBC. Interleukin-23, which characterized the imbalanced cytokine profile, may play an essential role in Th17-related human autoimmunity.
“…In the early immune response, cross-talk between T cells and antigen-presenting cells initiate the production of certain patterns of cytokines, which was dictated by the type of invaded antigen, and orchestrates the subsequent development of CD4+T cell subsets [13]. Each subset plays a unique role in the elimination of invaded antigen, and dysregulated subset differentiation has long been associated with disease [29,30]. In the present study we demonstrated a Th17/Treg-related cytokine profile in patients with PBC with significant increases in IL-1b, IL-6 and IL-23, which were theoretically prone to Th17 differentiations and averse to Treg differentiation.…”
SummaryPrimary biliary cirrhosis (PBC) is an organ-specific autoimmune liver disease characterized by progressive loss of intrahepatic small bile ducts. Cellular immune mechanisms involving T cell reaction are thought to be involved significantly in the pathogenesis of PBC. Recent studies have independently revealed enhanced T helper type 17 (Th17) response and weakened T regulatory cell (Treg) response in some autoimmune diseases, indicating a role of Th17/Treg imbalance in the pathogenesis of autoimmunity. This prompted us to investigate whether the Th17/Treg balance was broken in the peripheral blood of patients with PBC and, if it was, what cytokine circumstances might contribute to this imbalance. The expression of 11 Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 36 patients with PBC, 28 patients with chronic hepatitis B and 28 healthy controls were measured by real-time quantitativepolymerase chain reaction and enzyme-linked immunosorbent assay respectively. Peripheral Th17 and Treg cells were analysed by flow cytometry. Th17-related cytokines were increased significantly in patients with PBC. Consistent with the cytokine profile, the Th17 cell population and retinoidrelated orphan receptor gt expression were increased markedly. In contrast, the Treg cell population and forkhead box P3 expression were decreased dramatically in the peripheral blood of patients with PBC. Our study revealed that the Th17/Treg imbalance, both cytokine profile and cell numbers, exists in patients with PBC, suggesting its potential role in the breakdown of immune self-tolerance in PBC. Interleukin-23, which characterized the imbalanced cytokine profile, may play an essential role in Th17-related human autoimmunity.
“…8,11 But the recruitment of CD4 T lymphocytes cells into connective tissue might be responsible for the reduction of the number of these cells in peripheral blood. 16 Further studies are required to evaluate the role of these cells in graft survival.…”
CD4 T lymphocytes play a central role in allergic reactions. Thus the present study aimed to, immunohistochemically, evaluate the presence of these lymphocytes in rabbit gingival tissues after the replacement of Cenobone. This experimental one way blinded study was performed on 20 gingival tissues gathered from disease-free rabbits with or without bone powder, respectively groups A and B. Immunohistochemical envision method was performed for mapping CD4 lymphocytes. The number and intensity of staining were compared between groups in 5 consequent HPF without overlap with the light microscope in connective tissue. Data were analyzed by Fisher exact test, Wilcoxon, and chi-square statistically in SPSS20 software. The number of CD4 T cells was higher in group A compared to group B.(P=0.02) Pattern of distribution in connective tissue did not show a difference between the two groups. (P=0.41). Results of the present study might confirm the role of CD4 T in an allergic reaction to bone powder material and suggest this cell as a useful factor for the prediction of allergic reactions in the first weeks of surgery. Further studies in this field are required.
“…Treg cells directly contact or secrete suppressive cytokines that suppress inflammation ( 26 , 27 ). Each subset plays a unique role, and the dysregulation of subset differentiation has been associated with disease ( 28 , 29 ). An imbalance between Th17/Treg cells has been reported in the progression of atherosclerosis ( 30 ).…”
MicroRNAs (miRNAs or miRs) are small, non-coding RNA molecules that play significant roles in numerous diseases. However, there is limited information regarding the plasma expression of miRNAs in patients with primary biliary cirrhosis (PBC) as well as the potential role of miRNAs in the development of PBC. miRNA microarray analysis was performed using plasma obtaind from three patients with PBC and three healthy controls. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the differential expression of miRNAs in the plasma and peripheral blood mononuclear cells (PBMCs) isolated from 20 patients with PBC, 20 patients with chronic hepatitis B (CHB) and 20 healthy controls. These miRNAs in PBMCs and plasma were validated by linear regression analyses. The T cell subset frequency was analyzed by flow cytometry. Correlations between altered miRNA expression and the frequency of the T cell subsets were determined by linear regression analyses. The co-expression of miRNAs and IL-17A was examined using fluorescence in situ hybridization (FISH) and immunohistochemistry. The microarray analysis identified sixteen miRNAs that were differentially expressed. Four miRNAs were validated by RT-qPCR. The expression pattern of miR-572 and miR-92a in the PBMCs correlated with the expression pattern in plasma. We also found that miR-92a expression closely correlated with the frequency of a subset of IL-17-producing T helper cells (Th17), and that miR-92a was co-expressed with IL-17A in patients with PBC. Taken together, these findings revealed that plasma from patients with PBC has a unique miRNA expression profile. Moreover, miR-92a may play an important role in the pathogenesis of PBC by regulating Th17 cell differentiation.
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