T Helper Cell Subsets in the Pleural Fluid of Tuberculous Patients Differentiate Patients With Non-Tuberculous Pleural Effusions

BackgroundTuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis (Tb). Patients with TPE or malignant pleural effusions (MPE) frequently have a similar lymphocytic pleural fluid profile. Since the etiology of PE in various diseases is different, identifying the cellular components may provide diagnostic clues for understanding the pathogenesis.ObjectiveWe determined the frequency of T helper (Th) subtypes in the PEs for differentiation of Tb and non-Tb patients.MethodsThirty patients with TPE, 30 patients with MPE, 14 patients with empyema (EMP), and 14 patients with parapneumonic effusion (PPE) were enrolled between December 2018 and December 2019. Five-milliliter fresh PE in tubes containing heparin as an anticoagulant was obtained from patients. The frequencies of CD4+IL-9+, CD4+IL-22+, CD+IL-17+, and regulatory T-cells CD4+CD25+ FOXP3+ (Treg) were determined by flow cytometry.ResultsTreg cells have a lower frequency in TPE patients [4.2 (0.362–17.24)] compared with non-TPE patients [26.3 (3.349–76.93, p < 0.0001)]. The frequency of CD4+IL-9+ cells was significantly lower in TPE patients [3.67 (0.87–47.83)] compared with non-TPE groups [13.05 (1.67–61.45), p < 0.0001]. On the contrary, there was no significant difference in the frequency of CD4+IL-17+ and CD4+IL-22+ cells between TPE and non-TPE patients (p = 0.906 and p = 0.2188). Receiver-operator curve (ROC) analysis demonstrated that CD4+CD25+FOXP3+ T cells [optimal cutoff value = 13.6 (%), sensitivity 90%, specificity 75.86%] could be considered as predictor for TPE. However, adenosine deaminase [cutoff value 27.5 (IU/l), sensitivity 90%, specificity 96.5%] levels had an even greater predictive capacity.ConclusionADA, Treg cells, and CD4+IL-9+ cells may differentiate TPE from non-TPE patients. However, these results need validation in an independent large cohort.

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Immunostimulation During and After R-CHOP Therapy for B-Cell Lymphoma

Journal of Clinical & Experimental Immunology ◽

10.33140/jcei.01.01.07 ◽

2016 ◽

Vol 01 (01) ◽

Keyword(s):

T Cells ◽

B Cell ◽

Tumor Immunity ◽

Cd8 T Cells ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Treg Cells ◽

T Cell Subsets ◽

T Helper ◽

Chop Therapy

Backgrounds: Many studies show an immune imbalance in the tumor environment; some reports show that the T helper 1 (Th1)/ T helper 2 (Th2) ratio, the number of regulatory T-cells (Treg cells) or CD8+T-cells, and the CD8+Tcell/Treg cell ratio are associated with tumor suppression and expansion. Additionally, chemotherapy was reported to affect the immunity of patients with malignancy. Patients and Methods: Using flow cytometry we measured peripheral blood lymphocytes including non T-cells, as well as T-cell subsets such as CD3+T-cells, CD4+T-cells, CD8+T-cells, Treg cells, Th1 cells and Th2 cells before treatment, at the fourth cycle, and at 1, 3, 6 and 12 months after treatment in 21 patients with B-cell lymphoma receiving R-CHOP therapy. We also analyzed the changes in three immune indexes that reflect anti-tumor immunity (the CD4/CD8 ratio, the CD8/Treg ratio and the Th1/Th2 ratio). Results: Compared to pre-treatment there were significant decreases in the CD4/CD8 ratio between 1 month and 12 months after treatment (p<0.001, for all time points). The CD8/Treg ratio gradually increased with treatment with significant increases observed at 6 months (p=0.009) and 12 months after treatment (p=0.002). The Th1/ Th2 ratio showed a significant increase only before 4 cycles of therapy (p=0.007). Conclusion: Based on the changes in these three immune indexes, we propose that anti-tumor immunity improved after R-CHOP therapy, which enhanced the efficacy of R-CHOP therapy for lymphoma as well as its direct cytotoxic activity

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Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms20184323 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4323 ◽

Cited By ~ 10

Author(s):

Salvo Danilo Lombardo ◽

Emanuela Mazzon ◽

Maria Sofia Basile ◽

Giorgia Campo ◽

Federica Corsico ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

T Cell ◽

Immune Responses ◽

Cancer Metastasis ◽

Treg Cells ◽

T Helper ◽

Autoimmune Encephalomyelitis ◽

Healthy Donors

Tetraspanins are a conserved family of proteins involved in a number of biological processes including, cell–cell interactions, fertility, cancer metastasis and immune responses. It has previously been shown that TSPAN32 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferative T cells. Here, we show that TSPAN32 is expressed at higher levels in the lymphoid lineage as compared to myeloid cells. In vitro activation of T helper cells via anti-CD3/CD28 is associated with a significant downregulation of TSPAN32. Interestingly, engagement of CD3 is sufficient to modulate TSPAN32 expression, and its effect is potentiated by costimulation with anti-CD28, but not anti-CTLA4, -ICOS nor -PD1. Accordingly, we measured the transcriptomic levels of TSPAN32 in polarized T cells under Th1 and Th2 conditions and TSPAN32 resulted significantly reduced as compared with unstimulated cells. On the other hand, in Treg cells, TSPAN32 underwent minor changes upon activation. The in vitro data were finally translated into the context of multiple sclerosis (MS). Encephalitogenic T cells from Myelin Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis (EAE) mice showed significantly lower levels of TSPAN32 and increased levels of CD9, CD53, CD82 and CD151. Similarly, in vitro-activated circulating CD4 T cells from MS patients showed lower levels of TSPAN32 as compared with cells from healthy donors. Overall, these data suggest an immunoregulatory role for TSPAN32 in T helper immune response and may represent a target of future immunoregulatory therapies for T cell-mediated autoimmune diseases.

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T Helper 17 Cells in Autoimmune Liver Diseases

Clinical and Developmental Immunology ◽

10.1155/2013/607073 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Masanori Abe ◽

Yoichi Hiasa ◽

Morikazu Onji

Keyword(s):

T Cells ◽

Immune Responses ◽

Autoimmune Diseases ◽

Th17 Cells ◽

Transforming Growth Factor ◽

Treg Cells ◽

Reciprocal Relationship ◽

Th2 Cells ◽

T Helper ◽

T Helper 17

Many autoimmune diseases are driven by self-reactive T helper (Th) cells. A new population of effector CD4+T cells characterized by the secretion of interleukin (IL)-17, referred to as Th17 cells, has been demonstrated to be phenotypically, functionally, and developmentally distinct from Th1 and Th2 cells. Because the liver is known to be an important source of transforming growth factor-βand IL-6, which are cytokines that are crucial for Th17 differentiation, it is very likely that Th17 cells contribute to liver inflammation and autoimmunity. In contrast, another distinct subset of T cells, regulatory T cells (Treg), downregulate immune responses and play an important role in maintaining self-tolerance. In addition, there is a reciprocal relationship between Th17 cells and Tregs, in development and effector functions, and the balance between Th17 and Treg cells can affect the outcome of immune responses, particularly in autoimmune diseases. In this review, we will focus on the latest investigative findings related to Th17 cells in autoimmune liver disease.

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Evaluation of IL-17 Producing Memory Regulatory and Effector T Cells Expressing CD26 Molecule in Patients with Psoriasis

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v17i5.303 ◽

2018 ◽

pp. 453-463

Author(s):

Behnaz Esmaeili ◽

Parvin Mansouri ◽

Alipasha Meysamie ◽

Maryam Izad

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Cd4 T Cells ◽

Memory T Cells ◽

Treg Cells ◽

Effector Memory ◽

Forkhead Box P3 ◽

Forkhead Box ◽

Significant Difference ◽

Cytokine Levels

Memory regulatory T cells (Tregs) has been demonstrated to produce IL-17 in Psoriasis. Forkhead box P3 (Foxp3) has been demonstrated not to be reliable marker to evaluate Treg cells. Effector CD4+T cells also express Foxp3 after activation. Human T helper-17 cells (Th-17) express high level of surface CD26, while regulatory T cells are CD26 negative or low and this phenotype is stable even after activation of Treg cells. In this study, we aimed to analyze IL-17 producing Treg cells using CD26. Memory T cells were isolated from 10 patients with psoriasis and 10 controls. Ex vivo stimulated IL-17 producing regulatory (Forkhead Box P3 (Foxp3)+CD25+CD26-/low) and effector (Foxp3+CD25+CD26hi) memory T cells were analyzed by flow cytometry. IL-23, IL-6, TNFα, TGFβ and IL-17 cytokine levels were also evaluated. No significant difference in IL-17+memory regulatory T cells was seen between patients and controls (p=0.19). A significant decrease in the percentage of IL-17 producing CD26hi effector memory T cells was observed in patients (p=0.04). However, the percentage of these cells was not different between patients with mild or severe form of psoriasis compared to controls (p=0.13). We could not find any significant difference regarding IL-23, IL-6, TNFα, TGFβ and IL-17 cytokine levels in plasma and cell culture supernatant samples between patients and controls. Taken together, our results showed a reduced IL-17 producing effector memory CD26hi T cells in patients with psoriasis compared to controls. However, IL-17 producing memory regulatory CD4+T cells of patients showed no significant difference from that of controls

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The Effect of CCCP on Mitophagy in CD4+CD25+ Regulatory T Cells in Human Peripheral Blood

10.21203/rs.3.rs-38918/v1 ◽

2020 ◽

Author(s):

Yu-Jie Yang ◽

Md Rezaul Karim ◽

Jang Yuan ◽

Xiao-Qian Peng ◽

Pei Zeng ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Mitochondrial Membrane ◽

Human Peripheral Blood ◽

Treg Cells ◽

Oxygen Species ◽

Orange Yellow ◽

Significant Difference

Abstract Objective: To investigate the effects and mechanisms of different concentrations of CCCP on mitophagy in human peripheral blood regulatory T cells. Methods: Tregs were isolated, identified, and then grouped, treating with CCCP at a concentration of 2.5 μM, 5 μM, 10 μM, 20 μM and 40 μM for 24h in an incubator. Flow cytometry detected the reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial quality, and fluorescence microscopy observed the co-localization of mitochondria and lysosomes in each group. Results: The purity of CD4+CD25+Tregs was (93.36 ± 1.87) %. With the increase of CCCP concentration, the ROS level gradually increased, while the MMP decreased gradually. About the mitochondria and lysosome fusion, the fluorescence intensity of orange (yellow) was the highest when the concentration of CCCP was in the range of 5-10 μM while decreased with the CCCP concentration continually increasing. The mitochondrial quality decreased with the increase of CCCP concentration. However, there was no significant difference between groups C, D and E. The mitochondrial quality of groups F and G were significantly lower than that of group E. Conclusions: With the concentration of CCCP gradually increased, the level of ROS in Treg cells increased, and MMP decreased, which promoted the mitophagy, mitochondrial quality maintains homeostasis. When ROS accumulated, and MMP decreased significantly, the mitophagy was inhibited, and the mitochondrial quality decreased significantly.

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Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis

BMC Infectious Diseases ◽

10.1186/s12879-021-06730-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hua-Li Sun ◽

Xiu-Fang Du ◽

Yun-Xia Tang ◽

Guo-Qiang Li ◽

Si-Yuan Yang ◽

...

Keyword(s):

T Cells ◽

Immune Checkpoint ◽

Treg Cells ◽

Shanxi Province ◽

Healthy Controls ◽

Chronic Patients ◽

Immune Checkpoint Molecules ◽

Significant Difference ◽

Acute Patients ◽

Tgf Β1

Abstract Background The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. Methods Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People’s Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-β1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. Results The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-β1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-β1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). Conclusions Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-β1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

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Melatonin, an Endogenous Hormone, Modulates Th17 Cells via the Reactive Oxygen Species/TXNIP/HIF-1α Axis to Alleviate Autoimmune Uveitis

10.21203/rs.3.rs-1192974/v1 ◽

2022 ◽

Author(s):

Dan Liang ◽

Jun Huang ◽

Zhuang Li ◽

Yunwei Hu ◽

Zuoyi Li ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Flow Cytometry ◽

T Cells ◽

Th17 Cells ◽

Reactive Oxygen ◽

Treg Cells ◽

Oxygen Species ◽

T Helper ◽

Autoimmune Uveitis

Abstract Background Melatonin, an indoleamine produced by the pineal gland, plays a pivotal role in maintaining circadian rhythm homeostasis. Recently, the strong antioxidant and anti-inflammatory properties of melatonin have attracted attention of researchers. We evaluated the therapeutic efficacy of melatonin in experimental autoimmune uveitis (EAU), which is a representative animal model of human autoimmune uveitis. Methods EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 1-20 (IRBP1−20). melatonin was then administered via intraperitoneal injection to induce protection against EAU. With EAU induction for 14 days, clinical and histopathological scores were employed to evaluate the disease progression. T lymphocytes accumulation, the expression of inflammatory cytokines in the retinas were assessed via flow cytometry and RT-PCR. In vivo and in vitro experiments, T helper 1 (Th1), T helper 17 (Th17) and regulatory T (Treg) cells were detected via flow cytometry, the level reactive oxygen species(ROS) from CD4+ cells were tested via flow cytometry, and the expression of thioredoxin-interacting protein (TXNIP) and hypoxia-inducible factor 1 alpha (HIF-1α)proteins were also quantified via western blot analysis, to elucidate the mechanism of melatonin inhibiting EAU. Results Melatonin treatment resulted in notable attenuation of ocular inflammation in EAU mice, evidenced by decreasing optic disc edema, few signs of retinal vasculitis, and minimal retinal and choroidal infiltrates. Mechanistic studies revealed that melatonin restricted the proliferation of peripheral Th1 and Th17 cells and potentiated Treg cells by suppressing their transcription factors. In vitro studies corroborated that melatonin restrains the polarization of retina-specific T cells towards Th17 and Th1 cells in addition to enhancing the proportion of Treg cells. Pretreatment of retina-specific T cells with melatonin failed to induce EAU in naïve recipients. Furthermore, the ROS/ TXNIP/ HIF-1α pathway was shown to mediate the therapeutic effect of melatonin in EAU. Conclusions Melatonin regulates autoimmune T cells by restraining effector T cells and facilitating Treg generation, indicating that melatonin could be a hopeful treatment alternative for autoimmune uveitis.

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Influences of High-Dose Dexamethasone on Regulatory T Cells, Transforming Growth Factor-β1 and Interleukin-10 of Patients with Chronic ITP.

Blood ◽

10.1182/blood.v110.11.3920.3920 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3920-3920

Author(s):

Yun Ling ◽

Xiangshan Cao ◽

Ziqiang Yu ◽

Changgeng Ruan

Keyword(s):

T Cells ◽

Transforming Growth Factor ◽

Interleukin 10 ◽

Treg Cells ◽

Transforming Growth Factor Β1 ◽

High Dose ◽

Chronic Itp ◽

High Dose Dexamethasone ◽

Significant Difference ◽

Tgf Β1

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disorder and high-dose dexamethasone (HD-DXM) has been used as a first-line therapy for patients with ITP. However, little is known about the role of CD4+CD25 + regulatory T (Treg) cells, interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in the pathogenesis of chronic ITP and the effects of HD-DXM on them contained Treg cells, IL-10 and TGF-β1. In this study, we investigated the expressions of Treg cells, IL-10 and TGF-β1 in 26 untreated adult patients with chronic ITP. All patients had thrombocytopenia (platelet count <50 × 109/L) for more than 6 months. We also observed short time changes of Treg cells, IL-10 and TGF-β1 after treatment with HD-DXM in these patients. The results showed that a good initial response to HD-DXM occurred in 24 of the 26 patients with chronic ITP (92.3%): the mean platelet count was (84.9±30.4)×109/L [range, (20∼150) ×109/L] one week after the initiation of treatment. The proportion of CD4+CD25+ T cells in the peripheral blood of patients with chronic ITP was significantly higher than that in normal controls(P<0.001); there was no significant difference in the percentage of CD4+CD25high T cells between patients and controls ( P=0.317); but the number of CD4+ FOXP3+ T cells in patients was significantly lower than that in controls (P<0.001). After 4-days treatment with HD-DXM, the numbers of CD4+ CD25+ T cells (P<0.001), CD4+CD25high T cells ( P<0.001), and CD4+FOXP3+ T cells ( P<0.001) in patients were all significantly increased. In the serum of chronic ITP patients, the expression level of TGF-β1 was lower than that of healthy controls (P<0.0001) and HD-DXM could significantly increase it; there was no significant difference in the expression level of IL-10 between patients and controls ( P>0.05) and there was no remarkable change of IL-10 in patients after HD-DXM treatment (P>0.05). The mRNA levels of Foxp3 and TGF-β1 gene in patients were lower than those of controls (P<0.05 and P<0.05); HD-DXM administration significantly increased the expressions of Foxp3 and TGF-β1 gene(P<0.05 and P<0.0001), which were even higher than those of controls(P<0.05 and P<0.05); There was a positive correlation between the Foxp3 mRNA expression and TGF-β1 after treatment with HD-DXM (r =0.403, P=0.041). These results suggest that Foxp3 and TGF-β1 gene are deficient in chronic ITP and the immunosuppressive therapy of glucocorticoids could improve the expression levels of these genes.

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Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart

Scientific Reports ◽

10.1038/srep20077 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 17

Author(s):

Jiangping Song ◽

Jie Huang ◽

Xiao Chen ◽

Xiao Teng ◽

Zhizhao Song ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Regulatory T Cells ◽

Cardiac Transplantation ◽

Transforming Growth Factor ◽

Treg Cells ◽

Mouse Serum ◽

T Helper ◽

Immune Inflammation ◽

Head Protein

Abstract To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-specific T helper (Th)2 pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1a; the latter induced CD4+ T cells to express Fork head protein-3 and transforming growth factor (TGF)-β via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4+ T cells. Administration with the donor-derived exosomes significantly prolonged the allograft heart survival. We conclude that the donor-derived peripheral exosomes have the capacity to inhibit the immune inflammation in the allograft heart via inducing specific Treg cells, implicating that administration with the donor-derived exosomes may be beneficial to cardiac transplantation.

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Electroacupuncture Alleviates Intraoperative Immunosuppression in Patients Undergoing Supratentorial Craniotomy

Acupuncture in Medicine ◽

10.1136/acupmed-2012-010254 ◽

2013 ◽

Vol 31 (1) ◽

pp. 51-56 ◽

Cited By ~ 12

Author(s):

Guoyan Li ◽

Shuqin Li ◽

Lixin An ◽

Baoguo Wang

Keyword(s):

T Cells ◽

Immune Cell ◽

Dynamic Equilibrium ◽

Sham Acupuncture ◽

Full Blood Count ◽

Significant Difference ◽

Factor Α ◽

Induction Of Anaesthesia ◽

Cellular Components ◽

The Impact

Background Clinical experience suggests that anaesthesia using a combination of acupuncture and drugs can reduce the dosage of anaesthetics required for craniotomy, decreasing both the disturbance in physiological functions during the operation and postoperative complications and improving the rate of recovery. The aim of the present study was to investigate the impact of electroacupuncture (EA) on the dynamic equilibrium of the immune system and immune cell populations during the pericraniotomy period. Methods A total of 56 patients undergoing craniotomy were randomised into three groups: control (C, n=18), EA (A, n=19) and sham acupuncture (S, n=19) groups. Blood samples were collected before anaesthesia (T0) and 30 min, 2 h and 4 h after induction of anaesthesia (T1, T2 and T3, respectively,) to measure the levels of tumour necrosis factor α (TNFα), interleukin (IL)-8, IL-10, IgM, IgA, IgG and full blood count. Results There was no significant difference between the measurements in groups A and S during craniotomy. The levels of IgM and IgA decreased significantly in group C compared with groups A and S at T2 and T3 time points. The levels of total T cells and suppressor T cells in group C decreased significantly compared with groups A and S at T1 and T2, and the level of natural killer cells in group C decreased significantly compared with groups A and S at T1. No significant differences between groups were found in the levels of TNFα, IgG, IL-10, IL-8, leucocytes, neutrophils, monocytes, Th cells or B cells. Conclusions EA appears to reduce immunosuppression of both the humoral and cellular components during surgery.

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