Analysis of CD4+CD25hi Regulatory T Cells in the Peripheral Blood of Patients with B Cell Chronic Lymphocytic Leukemia (CLL).

Abstract Introduction: Naturally occurring regulatory T cells (Treg) prevent autoimmune and inflammatory diseases and represent one important factor contributing to the inhibition of antitumor immune response in cancer. CLL is a disease that is characterized both by immunodeficiency and sometimes by autoimmunity. We analyzed the frequency of Treg population in the peripheral blood of patients with B-CLL and correlated them with clinical and laboratory characteristics. Methods: We analyzed prospectively 49 patients with B-CLL (29 males, 20 females) with median age of 63 and 24 normal healthy volunteers. Freshly isolated peripheral blood mononuclear cells were analysed by flow cytometry using the EPICS XL /MSL cytometer (Beckman Coulter Co). We determined the level of apoptosis by the method of annexin-V and the frequency of Treg as cells positive for CD4, CD25hi and intracellular staining of Foxp3 using the PE anti-Human Foxp3 staining set protocol. We recorded clinical information regarding Rai and Binet staging, hematological and biochemical parameters and the presence of autoimmune hemolytic anemia. Results: The level of apoptosis as determined by the annexin V method was significantly lower on CD19+ cells of patients compared to normal controls (4.7 vs11.34 p=0.02). Moreover patients under treatment had significantly lower apoptosis level vs untreated (4vs6.4, p=0.023). The mean and median values of Treg cells in patients with CLL were higher but not significantly compared to controls. However the log10 values of the Treg frequencies were significantly higher in the group of CLL (0.6287vs0.1021, p=0.03). There was not any statistically significant association of Tregs with age, Rai and Binet staging, LDH values, and the level of apoptosis. Patients with levels of Treg cells>mean control value presented lower median expression of CD38 antigen of borderline significance (3.8vs7, p=0,06). 5/26 patients with Treg frequency >median control value presented autoimmune hemolytic anemia compared to 0/18 with Treg <median control value (p=0.06) Conclusion: The log10 values of Treg frequencies in patients with B-CLL were significantly higher compared to normal controls in accordance with previously published data. We did not observe any significant association with any laboratory or clinical characteristics or the level of apoptosis. Patients with Treg levels above the mean control values had a lower although not significantly expression of CD38 antigen indicating an association with more indolent disease. Functional study of these cells will help the interpretation of the data and will shed more light on the their exact role in the pathogenesis of the disease.

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Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽

10.3390/life11030245 ◽

2021 ◽

Vol 11 (3) ◽

pp. 245

Author(s):

Daniil Shevyrev ◽

Valeriy Tereshchenko ◽

Elena Blinova ◽

Nadezda Knauer ◽

Ekaterina Pashkina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Autoimmune Diseases ◽

Peripheral Blood ◽

Treg Cells ◽

Homeostatic Proliferation ◽

Suppressive Activity ◽

Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

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Quantitative and Qualitative Analysis Of Regulatory T Cells (Tregs) Derived From The Peripheral Blood Of Chronic Lymphocytic Leukemia Patients

Blood ◽

10.1182/blood.v122.21.5280.5280 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5280-5280

Author(s):

Eleni Dikaia Ioannidou ◽

Vassiliki Mpakou ◽

Myrofora Vikentiou ◽

Eugenia Konsta ◽

Frieda Kontsioti ◽

...

Keyword(s):

T Cells ◽

B Cell ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Annexin V ◽

Treg Cells ◽

Lymphocytic Leukemia ◽

Effector Cells ◽

T Effector Cells ◽

Healthy Donors

Abstract Introduction T regulatory cells are immunosuppressive cells, which are considered to play an important role in the regulation of immune response to cancer, by restraining autoreactive lymphocytes. Several studies, mostly in solid tumors, revealed that the number of Treg cells increases as the disease progresses and that Treg cells act by suppressing anti-tumor immune response, through the targeting of other immune cells, such as T cells, B cells and dendritic cells. Chronic lymphocytic leukemia (CLL) is a lymphoid malignancy, characterized by both, immunodeficiency and autoimmune disorders. Accumulated data indicate the role of T cells in the pathogenesis and development of CLL and reveal an increased number of Treg cells in CLL patients. The scope of this study is the analysis of the functional role of Tregs derived from the peripheral blood of CLL patients, mainly on B-CLL cells, and its correlation with well known prognostic factors. Methods Treg cells derived from mononuclear cells of 28 untreated B-cell CLL patients with a median age 62 (44-88) and 17 healthy donors were analyzed through Flow cytometry. Patients were classified according to Rai classification as Rai I:19, Rai II:4, Rai III:5 and according to Binet as Binet A: 24, Binet B:3 and Binet C:1. The following antibodies were used for the fluorescence-activated cell sorter (FACS) analysis: 1. CD45Ro-FITC/CD45RA-PE/CD4-ECD/CD25-PC5/CD127-PC7 2. CD1a-FITC/CD137-PE/CD4-ECD/CD25-PC5/CD127-PC7 3. CD95-FITC/cyCD152-PE/CD4-ECD/CD25-PC5/CD127-PC7 4. beads/FoxP3-PE/CD4-ECD/CD25-PC5/CD127-PC7 5. Annexin V-FITC/CD4-ECD/CD25-PC5/CD127-PC7 Moreover, peripheral blood was obtained from 15 patients with B-cell CLL. Mononuclear cells were isolated using Ficoll-Paque gradient centrifugation. CD4+CD25+ (Treg cells), CD4+CD25- (T effectοr cells, Teff), CD5+CD19+ (B-CLL) and CD5+CD19- (Normal B, NB) cells were separated using magnetic antibody cell sorting. To test the functionality of the assayed Tregs, the isolated cell populations were cultured in a 96-well plate (Tregs, Teff, B-CLL, NB cells, Tregs:Teff in a 4:1 ratio, B-cll:Tregs in 1:20 ratio, B-cll:Teff in 1:20 ratio, NB cells:Tregs in 1:20 ratio, NB cells:Teff in 1:20 ratio) and their proliferative capacity was measured using the BrdU assay. Results FACS analysis of the Treg cells resulted at the following observations: (1) The co-expression of the CD45RA-CD45RO markers was significantly higher in patients’ samples than in controls (p=0.047). (2) No significant differences were observed between patients and controls, regarding the expression of the CD1α marker, as well as the expression of CD95 and CD152 markers. (3) The Treg absolute cell number (cells/μL), estimated either as the number of CD4+ CD25+ CD127- cells or as the number of CD4+ CD25+ FoxP3+ cells, was statistically significantly higher in patients’ samples than in controls (CD127- p=0.047, FoxP3+ p= 0.036). (4) Annexin V expression in Treg cells from B- CLL patients was significantly lower compared to controls (p=0.027). Following the purification and culturing of T and B cells from B-cell CLL patients’ samples, functional analysis of the different cell populations was performed using the BrdU proliferation assay. We observed that Tregs were able to significantly suppress the proliferation of the Teff cells (p=0.002). After the co-culturing of NB cells (CD5+CD19-)and Tregs (CD4+CD25+) we found that NB cells seemed to significantly increase the proliferation of Treg cells, compared to the proliferation capacity of the Tregs when cultured alone (p=0.047). Moreover, we observed that Teff (CD4+CD25-) were able to significantly suppress the proliferation of B-CLL cells (CD5+CD19+), when co-cultured (B-CLL: Teff, 1:20 ratio) (p=0.05). Conclusions In B-cell CLL patients, Treg cells are significantly higher and present with lower apoptotic levels compared to healthy donors’ samples. The functional analysis of Treg cells indicates that they can effectively suppress the proliferation of T effector cells. Moreover, T effector cells seem to suppress the proliferation of B-CLL cells, while NB cells increase the proliferation of Treg cells. These observations could probably indicate that at the early stages of the disease, where NB cells are more aberrant, Treg cells’ activity is induced, leading to Teff cells’ suppression and therefore, to an indirect induction of B-CLL cells’ proliferation. Disclosures: No relevant conflicts of interest to declare.

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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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R404 – Regulatory T Cells and Clinical Outcome in HNSCC Patients

Otolaryngology ◽

10.1016/j.otohns.2008.05.558 ◽

2008 ◽

Vol 139 (2_suppl) ◽

pp. P178-P178

Author(s):

Osama Alhamarneh ◽

Nicholas D. Stafford ◽

John Greenman

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Clinical Outcome ◽

Treg Cell ◽

Cell Population ◽

Peripheral Blood ◽

Treg Cells ◽

Clinicopathological Parameters ◽

Pre Treatment ◽

Disease Stages

Problem To determine the correlation between peripheral blood CD4+CD25high regulatory T cells (Treg), a suppressor cell population that dampen the immune response, and clinical outcome and survival in HNSCC patients. Methods Treg cell numbers in the peripheral blood of newly-presenting, untreated HNSCC patients (n=65) were determined pre-operatively, 4–6 weeks after treatment (n=30) and in a cohort of healthy controls (n=35) of similar age and sex, after Treg cell isolation using magnetic microbeads (Miltenyi Biotec) by flow cytometry. The Mann-Whitney U test was used to analyse the correlations between Treg cell levels and clinical outcome. Results Treg cells were significantly higher in patients pre-operatively vs. controls (p=0.002). After treatment, patients showed a significant rise compared with their pre-treatment levels (p=0.022). Pre-treatment Treg cells levels did not correlate with survival or any of the other conventional clinicopathological parameters. However, higher Treg cells levels were discovered in the advanced disease stages (III/IV vs. I/II, median 6.3 vs 4.3) in the pre-treatment group that turned into significantly higher levels in the early disease stages post treatment (I/II vs. III/IV, median 10.8 vs. 5.67 p=0.044). Conclusion Although peripheral blood Treg cells levels were higher in patients when compared to controls, no correlation was found between this cell population and clinical outcome or survival. In contrast with gastric, colorectal and ovarian tumors, Treg cell levels did not normalize 4–6 weeks after curative treatment in this cohort of HNSCC patients. Studies into Treg cell function are thus required to try and elucidate the apparent paradox in Treg cell levels observed in HNSCC. Significance The presence of Regulatory T cells in the peripheral blood of HNSCC patients may be detrimental to host defence against tumor. Further studies are needed to explore their role in the tumor microenvironment and their correlation with clinical outcome.

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Study of the Quantity and Function of Regulatory T Cells In the Hemocytopenic Patients with Positive BMMNC-Coombs Test

Blood ◽

10.1182/blood.v116.21.4875.4875 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4875-4875

Author(s):

Rong Fu ◽

Jin Chen ◽

Zonghong Shao ◽

Jun Wang ◽

Lijuan Li ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Regulatory T Cells ◽

Conflicts Of Interest ◽

Treg Cells ◽

Cd4 Cells ◽

Healthy Donors ◽

Two Factors ◽

And Function ◽

Normal Controls

Abstract Abstract 4875 Objective To investigate the quantity and function of regulatory T cells in the IRP, then explore the significance of Treg cells in the pathogenesis of IRP. Methods Sixty-two patients with IRP and twenty-four healthy donors were enrolled in this study. The ratios of CD4+CD25+/CD4+ and CD4+CD25+CD127low/CD4+ in bone marrow were examined with flow cytometry. The levels of IL-2, ATGF-β were tested with ELISA. The expressions of FoxP3 and Galectin-10 mRNA in BMMNC were measured by semiquantitive RT-PCR. Results The levels of IL-2, ATGF-β in bone marrow of untreated or recovered IRP patients (5.64±1.70, 6.19±2.53; 1.79±0.67, 1.86±0.76) were significantly lower than them of normal controls (7.91±3.71,2.48±0.94) (p<0.05); The ratio of CD4+CD25+/CD4+ cells in bone marrow of untreated IRP patients (22.46±9.47) was significantly lower than that of recovered IRP patients or normal controls (27.10±7.08, 30.59±8.58) (p<0.05); The ratio of CD4+CD25+CD127low/CD4+ cells in bone marrow of untreated IRP patients (7.18±2.72) was significantly lower than that of recovered IRP patients or normal controls (9.07±4.67, 10.44±3.24) (p<0.05). The relative mRNA expressions of FoxP3 and galentin-10 were 0.34±0.25, 0.69±0.51, 0.82±0.65 and0.66±0.11, 0.74±0.11, 0.76±0.09 in three groups, respectively. The expressions of the two factors in untreated IRP patients were significantly lower than them in recovered IRP patients or normal controls (p<0.05). Conclusions There exist abnormalities in quantity and function of Treg cells in IRP patients which might play important role in the pathogenesis of IRP. Disclosures: No relevant conflicts of interest to declare.

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Quantification of Treg cells in peripheral blood and lymph nodes of dogs with multicentric lymphoma

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-4162-9599 ◽

2017 ◽

Vol 69 (6) ◽

pp. 1496-1502

Author(s):

L.A. Anai ◽

T.D. Munhoz ◽

L.M.S. Semolin ◽

N.P. Reis Filho ◽

E.M. Terra ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Lymph Nodes ◽

Peripheral Blood ◽

Treg Cells ◽

Control Group ◽

Significant Difference ◽

Healthy Dogs ◽

Multicentric Lymphoma

ABSTRACT Lymphoma is a malignant tumor characterized by cell proliferation of lymphoid origin and corresponds to 90% of all hematopoietic neoplasms of dogs. Regulatory T cells (Tregs) have been the target of many investigations in oncology due to their potential of down-regulating immune responses, as well as ensuring the maintenance of active mechanisms of tumor suppression. The aims of the present study were to compare the percentage of Tregs in peripheral blood between dogs with multicentric lymphoma and healthy animals, together with the percentage of Tregs in peripheral blood and lymph nodes of dogs with multicentric lymphoma. Twenty-six animals were enrolled in the study: 10 healthy dogs comprised the control group (CG) and 16 dogs with multicentric lymphoma comprised the Lymphoma Group (LG). We observed that dogs in the LG showed a significantly higher Tregs expression in peripheral blood compared to the CG. No significant difference was observed between Tregs expression in lymph nodes and peripheral blood of the LG, however. With these results, it is possible to conclude that multicentric lymphoma is a neoplasm with high Tregs expression, which poses this as a condition of interest when investigating treatments that can suppress Regulatory T cells.

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Altered Frequencies of CD4+ CD25+ Foxp3+ and CD8+ CD25+ Foxp3+ Regulatory T Cells in Pre-eclampsia

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v17i6.618 ◽

2019 ◽

Cited By ~ 2

Author(s):

Maryam Zare ◽

Mehrnoosh Doroudchi ◽

Behrouz Gharesi-Fard

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Regulatory T Cells ◽

Negative Correlation ◽

Peripheral Blood ◽

Pregnancy Complications ◽

Treg Cells ◽

Positive Correlation ◽

Blood Pressures ◽

In Pregnancy

Regulatory T cells are of utmost importance for tolerating the fetus. In some pregnancy complications such as pre-eclampsia, the frequency of CD4+CD25+Foxp3+ regulatory T cells is altered, but there is no consistency regarding the results. Besides, little is known about the frequency of CD8+CD25+Foxp3+ Treg cells in pregnancy complications. Therefore, we aimed to investigate the frequency of both CD4+ and CD8+ regulatory T cells in the peripheral blood of women afflicted by preeclampsia. Ten non-pregnant, ten healthy pregnant, and ten preeclamptic women participated in this study. Four colors flow cytometry method was used to identify the frequency of the CD4+ and CD8+ regulatory T cells in the peripheral blood. Results indicated that the frequencies of CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+ cells were significantly lower in preeclamptic women compared to healthy pregnant and non-pregnant ones (p<0.05). A positive correlation was also observed between CD4+ and CD8+ regulatory T cells (R=0.532, p=0.002). Moreover, CD4+ regulatory T cells negatively correlated with systolic and diastolic blood pressures (R=-0.760 and -0.753, respectively; p<0.001). CD8+ regulatory T cells also had a negative correlation with systolic (R=-0.503, p=0.001) and diastolic (R=-0.590, p=0.005) blood pressures. In conclusion, a reduction in the frequencies of both CD4+ CD25+ Foxp3+ and CD8+CD25+Foxp3+ regulatory T cells might be important in the pathogenesis of pre-eclampsia.

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CD4+CD25highCD127low/-FoxP3+ Regulatory T-Cell Population in Acute Leukemias: A Review of the Literature

Journal of Immunology Research ◽

10.1155/2019/2816498 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 4

Author(s):

M. Niedźwiecki ◽

O. Budziło ◽

E. Adamkiewicz-Drożyńska ◽

D. Pawlik-Gwozdecka ◽

M. Zieliński ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Lymphoblastic Leukemia ◽

Treg Cells ◽

Self Control ◽

Pharmacological Intervention ◽

Acute Leukemias ◽

Regulatory T Lymphocytes ◽

Immunological System

Regulatory T-cells (Tregs) are a very important subtype of lymphocytes when it comes to self-control in the human immunological system. Tregs are decisive not only in the protection against destruction of own tissues by autoimmune immunocompetent cells but also in the immunological answer to developing cancers. On the other hand, Tregs could be responsible for the progression of acute and chronic leukemias. In our study, we review publications available in the PUMED database concerning acute leukemia, with a particular emphasis on child’s leukemias. The percentage of regulatory T-lymphocytes in peripheral blood and bone marrow was elevated compared to those in healthy individuals and correlated with progressive disease. Regulatory T-cells taken from children diagnosed with leukemia showed a higher suppressive capability, which was confirmed by detecting elevated levels of secreted IL-10 and TGF-beta. The possibility of pharmacological intervention in the self-control of the immunological system is now under extensive investigation in many human cancers. Presumably, Treg cells could be a vital part of targeted therapies. Routine Treg determination could be used to assess the severity of disease and prognosis in children with acute lymphoblastic leukemia. This proposition results from the fact that in some studies, higher percentage of Treg cells in peripheral blood was demonstrated. However, observations confirming these facts are scarce; thus, extrapolating them to the population of children with hematological malignancies needs to be verified in additional studies.

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

10.20944/preprints202006.0094.v1 ◽

2020 ◽

Author(s):

Yu-Jie Yang ◽

Md Rezaul Karim ◽

Jiang Yuan ◽

Xiao-Qian Peng ◽

Pei Zeng ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Human Peripheral Blood ◽

Treg Cells ◽

Oxygen Species ◽

Orange Yellow ◽

M 10 ◽

Significant Difference

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 level of ROS 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 was significantly decreased.

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The Imbalance of FOXP3/GATA3 in Regulatory T Cells from the Peripheral Blood of Asthmatic Patients

Journal of Immunology Research ◽

10.1155/2018/3096183 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Tiantian Chen ◽

Xiaoxia Hou ◽

Yingmeng Ni ◽

Wei Du ◽

Huize Han ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Healthy Subjects ◽

Treg Cells ◽

Asthmatic Patients ◽

Proliferation Activity ◽

Healthy Control ◽

And Function

Background. Treg cells play an important role in the pathogenic progress of asthma. Objective. To address the alterations of Treg cells in asthma. Methods. Proliferation-and function-associated markers of Treg cells along with the percentage of Treg cells producing some cytokine from asthmatics and healthy subjects were analyzed by flow cytometry. Besides, the expressions of USP21 and PIM2 in Treg cells were measured by cell immunochemistry after Treg cells were sorted. Results. Treg cells from asthmatic patients showed lower proliferation activity and were more likely to be apoptotic. These cells expressed lower levels of GITR, CTLA-4, Nrp-1, and IL-10 compared to those from the healthy control. Th2-like Treg cells increased in asthmatic patients, while the percentage of IFN-r+ Treg cells was similar between two groups. Moreover, the percentage of IL-4+ Treg cells is related to the asthma control. Treg cells from asthmatic patients expressed more FOXP3 as well as GATA3; the expression level of GATA3 negatively correlated with FEV1%pred. Increased expressions of USP21 and PIM2 in Treg cells from asthmatic patients were found. Conclusion. Treg cells decreased in asthmatic patients, with an impaired immunosupression function and a Th2-like phenotype, which may be due to overexpression of GATA3 and FOXP3, regulated by USP21 and PIM2, respectively.

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