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1.
Alexis Mathian Romain Jouenne Driss Chader Fleur Cohen-Aubart Julien Haroche Jehane Fadlallah Laetitia Cla?r Lucile Musset Guy Gorochov Zahir Amoura Makoto Miyara 《PloS one》2015,10(12)
Background/Purpose
A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.Methods
We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.Results
Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.Conclusion
IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE. 相似文献2.
We focus on the role of CD8+ Treg cell in Intravenous methyl-prednisolone (IVMP) pulse therapy in forty patients with active Class III/IV childhood lupus nephritis (LN) with heavy proteinuria. IVMP therapy for five days. From peripheral blood mononuclear cells (PBMCs) and renal tissues, we saw IVMP therapy definitely restoring both CD4+CD25+FoxP3+ and CD8+CD25+Foxp3+ Treg cell number plus greater expression with intracellular IL-10 and granzyme B in CD8+FoxP3+ Treg from PBMCs. IVMP-treated CD8+CD25+ Treg cells directly suppressed CD4+ T proliferation and induced CD4+CD45RO+ apoptosis. Histologically, CD4+FoxP3+ as well as CD8+FoxP3+ Treg cells appeared in renal tissue of LN patients before IVMP by double immunohistochemical stain. CD8+FoxP3+ Treg cells increased in 10 follow-up renal biopsy specimens after IVMP. Reverse correlation of serum anti-C1q antibody and FoxP3+ Treg cells in PBMNCs (r = −0.714, P<0.01). After IVMP, serum anti-C1q antibody decrease accompanied increase of CD4+FoxP3+ Treg cells. CD8+Treg cells reduced interferon-r response in PBMCs to major peptide autoepitopes from nucleosomes after IVMP therapy; siRNA of FoxP3 suppressed granzyme B expression while decreasing CD8+CD25+Treg-induced CD4+CD45RO+ apoptosis. Renal activity of LN by SLEDAI-2k in childhood LN was significantly higher than two weeks after IVMP (P<0.01). CD8+FoxP3+ Treg cells return in post-IVMP therapy and exert crucial immune modulatory effect to control autoimmune response in LN.
Trial Registration
DMR97-IRB-259 相似文献3.
Giuseppe Nocentini Alessia Alunno Maria Grazia Petrillo Onelia Bistoni Elena Bartoloni Sara Caterbi Simona Ronchetti Graziella Migliorati Carlo Riccardi Roberto Gerli 《Arthritis research & therapy》2014,16(5)
Introduction
CD4+CD25low/-GITR+ T lymphocytes expressing forkhead box protein P3 (FoxP3) and showing regulatory activity have been recently described in healthy donors. The objective of the study was to evaluate the proportion of CD4+CD25low/-GITR+ T lymphocytes within CD4+ T cells and compare their phenotypic and functional profile with that of CD4+CD25highGITR− T lymphocytes in systemic lupus erythematosus (SLE) patients.Methods
The percentage of CD4+CD25low/-GITR+ cells circulating in the peripheral blood (PB) of 32 patients with SLE and 25 healthy controls was evaluated with flow cytometry. CD4+CD25low/-GITR+ cells were isolated with magnetic separation, and their phenotype was compared with that of CD4+CD25highGITR− cells. Regulatory activity of both cell subsets was tested in autologous and heterologous co-cultures after purification through a negative sorting strategy.Results
Results indicated that CD4+CD25low/-GITR+ cells are expanded in the PB of 50% of SLE patients. Expansion was observed only in patients with inactive disease. Phenotypic analysis demonstrated that CD4+CD25low/-GITR+ cells display regulatory T-cell (Treg) markers, including FoxP3, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), transforming growth factor-beta (TGF-β), and interleukin (IL)-10. In contrast, CD4+CD25highGITR− cells appear to be activated and express low levels of Treg markers. Functional experiments demonstrated that CD4+CD25low/-GITR+ cells exert a higher inhibitory activity against both autologous and heterologous cells as compared with CD4+CD25highGITR− cells. Suppression is independent of cell contact and is mediated by IL-10 and TGF-β.Conclusions
Phenotypic and functional data demonstrate that in SLE patients, CD4+CD25low/-GITR+ cells are fully active Treg cells, possibly representing peripheral Treg (pTreg) that are expanded in patients with inactive disease. These data may suggest a key role of this T-cell subset in the modulation of the abnormal immune response in SLE. Strategies aimed at expanding this Treg subset for therapeutic purpose deserve to be investigated. 相似文献4.
Wen-cai Zhang Jun Wang Yan-wen Shu Ting-ting Tang Zheng-feng Zhu Ni Xia Shao-fang Nie Juan Liu Su-feng Zhou Jing-jing Li Hong Xiao Jing Yuan Meng-yang Liao Long-xian Cheng Yu-hua Liao Xiang Cheng 《The Journal of biological chemistry》2012,287(41):34157-34166
Regulatory T (Treg) cells play a protective role against the development of atherosclerosis. Previous studies have revealed Treg cell defects in patients with non-ST elevation acute coronary syndrome (NSTACS), but the mechanisms underlying these defects remain unclear. In this study, we found that the numbers of peripheral blood CD4+CD25+CD127low Treg cells and CD4+CD25+CD127lowCD45RA+CD45RO− naive Treg cells were lower in the NSTACS patients than in the chronic stable angina (CSA) and the chest pain syndrome (CPS) patients. However, the number of CD4+CD25+CD127lowCD45RA−CD45RO+ memory Treg cells was comparable in all of the groups. The frequency of CD4+CD25+CD127lowCD45RO−CD45RA+CD31+ recent thymic emigrant Treg cells and the T cell receptor excision circle content of purified Treg cells were lower in the NSTACS patients than in the CSA patients and the CPS controls. The spontaneous apoptosis of Treg cells (defined as CD4+CD25+CD127lowannexin V+7-AAD−) was increased in the NSTACS patients compared with the CSA and CPS groups. Furthermore, oxidized LDL could induce Treg cell apoptosis, and the oxidized LDL levels were significantly higher in the NSTACS patients than in the CSA and CPS groups. In accordance with the altered Treg cell levels, the concentration of TNF-α was increased in the NSTACS patients, resulting in a decreased IL-10/TNF-α ratio. These findings indicate that the impaired thymic output of Treg cells and their enhanced susceptibility to apoptosis in the periphery were responsible for Treg cell defects observed in the NSTACS patients. 相似文献
5.
Timothy R. D. J. Radstake Lenny van Bon Jasper Broen Mark Wenink Kim Santegoets Yanhui Deng Anila Hussaini Robert Simms William W. Cruikshank Robert Lafyatis 《PloS one》2009,4(6)
Background
Regulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc).Methods/Principal Findings
Patients were subdivided as having limited cutaneous SSc (lcSSc, n = 20) or diffuse cutaneous SSc (dcSSc, n = 48). Further subdivision was made between early dcSSc (n = 24) and late dcSSc (n = 24) based upon the duration of disease. 26 controls were studied for comparison. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, FoxP3, CD127, CD62L, GITR, CD69 using flow cytometry. T cell suppression assays were performed using sorted CD4CD25highCD127- and CD4CD25lowCD127high and CD3+ cells. Suppressive function was correlated with CD69 surface expression and TGFβ secretion/expression. The frequency of CD4+CD25+ and CD25highFoxP3highCD127neg T cells was highly increased in all SSc subgroups. Although the expression of CD25 and GITR was comparable between groups, expression of CD62L and CD69 was dramatically lower in SSc patients, which correlated with a diminished suppressive function. Co-incubation of Tregs from healthy donors with plasma from SSc patients fully abrogated suppressive activity. Activation of Tregs from healthy donors or SSc patients with PHA significantly up regulated CD69 expression that could be inhibited by SSc plasma.Conclusions/Significance
These results indicate that soluble factors in SSc plasma inhibit Treg function specifically that is associated with altered Treg CD69 and TGFβ expression. These data suggest that a defective Treg function may underlie the immune dysfunction in systemic sclerosis. 相似文献6.
Georgina Thorborn Laura Pomeroy Heidi Isohanni Melissa Perry Barry Peters Annapurna Vyakarnam 《PloS one》2010,5(2)
Background
In HIV infection, uncontrolled immune activation and disease progression is attributed to declining CD4+CD25+FoxP3+ regulatory T-cell (Treg) numbers. However, qualitative aspects of Treg function in HIV infection, specifically the balance between Treg cell suppressive potency versus suppressibility of effector cells, remain poorly understood. This report addresses this issue.Methodology/Principal Findings
A classic suppression assay to measure CD4+CD45RO+CD25hi Treg cells to suppress the proliferation of CD4+CD45RO+CD25− effectors cells (E) following CD3/CD28 polyclonal stimulation was employed to compare the suppressive ability of healthy volunteers (N = 27) and chronic, asymptomatic, treatment naïve, HIV-infected subjects (N = 14). HIV-infected subjects displayed significantly elevated Treg-mediated suppression compared to healthy volunteers (p = 0.0047). Cross-over studies comparing Treg cell potency from HIV-infected versus control subjects to suppress the proliferation of a given population of allogeneic effector cells demonstrated increased sensitivity of CD4+CD25− effector cells from HIV-infected subjects to be suppressed, associated with reduced production of the Treg counter-regulatory cytokine, IL-17, rather than an increase in the suppressive potential of their CD4+CD25+ Treg cells. However, compared to controls, HIV+ subjects had significantly fewer absolute numbers of circulating CD4+CD25+FoxP3+ Treg cells. In vitro studies highlighted that one mechanism for this loss could be the preferential infection of Treg cells by HIV.Conclusions/Significance
Together, novel data is provided to support the contention that elevated Treg-mediated suppression may be a natural host response to HIV infection 相似文献7.
Ester Roos-Engstrand Jamshid Pourazar Annelie F Behndig Anders Bucht Anders Blomberg 《Respiratory research》2011,12(1):74
Background
Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.Method
Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.Results
In smokers with normal lung function, the expression of CD25+CD4+ was increased, whereas the proportions of FoxP3+ and CD127+ were unchanged compared to never-smokers. Among CD4+ cells expressing high levels of CD25, the proportion of FoxP3+ cells was decreased and the percentage of CD127+ was increased in smokers with normal lung function. CD4+CD25+ cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.Conclusion
The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells. Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25+ helper T-cell population in smokers and stable COPD. Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development. 相似文献8.
Andrew J. Rech Rosemarie Mick David E. Kaplan Kyong-Mi Chang Susan M. Domchek Robert H. Vonderheide 《Cancer immunology, immunotherapy : CII》2010,59(4):599-607
FoxP3
+
CD4
+
regulatory T cells (Tregs) are important mediators of peripheral immune tolerance, acting via multiple mechanisms to suppress
cellular immunity including antitumor responses. Although therapeutic strategies have been proposed to deplete Tregs in patients
with breast cancer and other malignancies, dynamic changes in the Treg compartment as a function of stage and treatment of
breast cancer remain poorly understood. Here, we evaluated peripheral blood CD4+ T cells and FoxP3+ CD4+ T cells from 45 patients with early or late stage breast cancer and compared percentages, absolute counts, and Treg function
to those from healthy volunteers (HV) of comparable age. Patients having completed adjuvant chemotherapy and patients with
metastatic cancer exhibited significantly lower absolute CD4 counts and significantly higher percentages of FoxP3+ CD4+ T cells. In contrast, the absolute counts of circulating FoxP3+ CD4+ T cells did not differ significantly among early stage patients, late stage patients, or HV. Functionally, FoxP3+ CD4+ T cells from all donor groups similarly expressed CTLA-4 and failed to secrete IFN-γ in response to stimulation. Thus, although
Tregs comprise an increased percentage of circulating CD4+ T cells in patients with metastatic breast cancer and patients in remission after completing the adjuvant chemotherapy, the
systemic Treg pool, as measured by absolute counts, appears relatively constant regardless of disease stage or treatment status.
Total CD4+ T cell counts are not constant, however, suggesting that homeostatic mechanisms, or susceptibility to cytotoxic or malignant
insults, fundamentally differ for regulatory and non-regulatory CD4+ T cells. 相似文献
9.
10.
Jang-Jaer Lee Chiou-Yueh Yeh Chiau-Jing Jung Ching-Wen Chen Mao-Kuang Du Hui-Ming Yu Chia-Ju Yang Hui-yi Lin Andy Sun Jenq-Yuh Ko Shih Jung Cheng Yen-Liang Chang Jean-San Chia 《PloS one》2014,9(1)
CD8+ T cells play important roles in anti-tumor immunity but distribution profile or functional characteristics of effector memory subsets during tumor progression are unclear. We found that, in oral squamous carcinoma patients, circulating CD8+ T cell pools skewed toward effector memory subsets with the distribution frequency of CCR7−CD45RA−CD8+ T cells and CCR7− CD45RA+CD8+ T cells negatively correlated with each other. A significantly higher frequency of CD127lo CCR7−CD45RA−CD8+ T cells or CCR7−CD45RA+CD8+ T cells among total CD8+ T cells was found in peripheral blood or tumor infiltrating lymphocytes, but not in regional lymph nodes. The CD127hi CCR7−CD45RA−CD8+ T cells or CCR7−CD45RA+CD8+ T cells maintained significantly higher IFN-γ, IL-2 productivity and ex vivo proliferative capacity, while the CD127lo CCR7−CD45RA−CD8+ T cells or CCR7−CD45RA+CD8+ T cells exhibited higher granzyme B productivity and susceptibility to activation induced cell death. A higher ratio of CCR7−CD45RA+CD8+ T cells to CCR7−CD45RA−CD8+ T cells was associated with advanced cancer staging and poor differentiation of tumor cells. Therefore, the CD127lo CCR7−CD45RA−CD8+ T cells and CCR7−CD45RA+CD8+ T cells are functionally similar CD8+ T cell subsets which exhibit late differentiated effector phenotypes and the shift of peripheral CD8+ effector memory balance toward CCR7−CD45RA+CD8+ T cells is associated with OSCC progression. 相似文献
11.
12.
Eva Pericolini Elena Gabrielli Alessia Alunno Elena Bartoloni Bocci Stefano Perito Siu-Kei Chow Elio Cenci Arturo Casadevall Roberto Gerli Anna Vecchiarelli 《PloS one》2014,9(10)
Objective
Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal).Methods
Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells.Results
GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25−FOXP3+ Treg cells; ii) increase intracellular levels of TGF-β1 in CD4+CD25−FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25−FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25−FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-γ and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production.Conclusion
These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25−FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases. 相似文献13.
Background
T-lymphocyte infiltration into colon carcinomas can influence clinical outcome, and interactions among T cell subsets may be more informative than either subset alone. Our objective was to examine the prognostic impact of tumor-infiltrating FoxP3+ regulatory T cells (Tregs) in relation to cytotoxic CD8+ T lymphocytes in patients with colon carcinomas characterized by DNA mismatch repair (MMR) status who participated in adjuvant chemotherapy trials.Methods
FoxP3+ and CD8+ densities in tumor epithelial and stromal compartments were analyzed by immunohistochemistry and quantified in resected, stage II and III colonic carcinomas (N = 216). Immune marker density was dichotomized at the median and categorized as high vs low. MMR status was classified as MMR deficient (dMMR) or proficient (pMMR). Cox models were adjusted for age, stage, and tumor grade.Results
The density of FoxP3+ infiltration was similar in tumor stroma and epithelia, whereas CD8+ was higher in stroma. The prognostic impact of FoxP3+ and CD8+ T cell infiltration was stronger in stroma vs epithelia, and the density of each marker in stroma was independently associated with improved overall survival (OS). However, the impact of FoxP3+ on survival was dependent upon CD8+ density (P interaction = .040). Among CD8+low tumors, FoxP3+high cases had significantly improved OS compared to FoxP3+low cases after adjustment for covariates (hazard ratio 0.43; 95% confidence interval 0.19 to 0.95; P = .030). In contrast, FoxP3+ was not prognostic among CD8+high tumors. FoxP3+ remained prognostic in CD8+low tumors after further adjustment for MMR or BRAF V600E mutation status. Additionally, these immune markers identified a pMMR subgroup with a similarly favorable OS as for dMMR tumors.Conclusions
The prognostic impact of FoxP3+ and CD8+ T cell density are inter-dependent, whereby FoxP3+ exerts a favorable influence on survival only in colon cancers with low CD8+ infiltration. 相似文献14.
Gleb Slobodin Mohammad Sheikh Ahmad Itzhak Rosner Michael Rozenbaum Elias Toubi 《Cellular immunology》2010,261(2):77-80
Background
The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc).Methods
Ten patients with SSc donated 20 ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4+ cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-β and IL-10 by activated CD4+ cells was measured by ELISA in culture supernatants.Results
The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r = 0.71, p = 0.034 and r = 0.67, p = 0.044, respectively). ELISA-measured production of TGF-β and IL-10 by CD4+ cells was similar in patients and controls.Conclusions
Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-β or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed. 相似文献15.
Anita Feichtenbeiner Matthias Haas Maike Büttner Gerhard G. Grabenbauer Rainer Fietkau Luitpold V. Distel 《Cancer immunology, immunotherapy : CII》2014,63(2):111-119
Purpose
In various cancer types, an abundance of FoxP3+ regulatory T cells (Treg) has been associated with an unfavorable outcome. Yet, the role of Treg on cancer immunity has been shown to be complex. In single cell marker technique, other tumor-infiltrating lymphocytes (TILs) such as cytotoxic CD8+ T cells (CTL) also influenced prognosis. This study for the first time investigates the concurrent spatial distribution pattern of CD8+ and FoxP3+ TILs and their prognostic impact in human gastric cancer.Materials and methods
Tumor tissue microarrays of 50 patients with surgically treated adenocarcinoma of the cardia were studied. An immunohistochemical double staining of CD8+ and FoxP3+ TILs was performed. Cell counts and cell-to-cell distances in tumor epithelium and stroma were evaluated with image-processing software. Metastasis-free survival, no-evidence-of-disease survival, and overall survival were investigated (mean follow-up time 6.9 years).Results
High intraepithelial infiltration of CD8+ and FoxP3+ TIL was associated with the improved 10-year metastasis-free survival (83 vs. 54 %, p = 0.04 and 85 vs. 59 %, p = 0.09, respectively). Considering cell-to-cell distance and comparing patients with functional (30–110 μm) versus nonfunctional distances of CD8+ and FoxP3+ TILs, 10-year survival rates differed between 89 and 55 % (p = 0.009), respectively.Conclusion
Prognostic influence of tumor-infiltrating immune cells in gastric cancer critically depends on their cell-to-cell distance. FoxP3+ TILs must be located within a distance between 30 and 110 μm of CD8+ T cells to positively impact on prognosis. 相似文献16.
Young Ah Lee Hang-Rae Kim Jeong Seon Lee Hae Woon Jung Hwa Young Kim Gyung Min Lee Jieun Lee Ji Hyun Sim Sae Jin Oh Doo Hyun Chung Choong Ho Shin Sei Won Yang 《PloS one》2015,10(12)
Objective
We investigated whether the frequency, phenotype, and suppressive function of CD4+FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls.Design and Methods
Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4–35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (–) (n = 7) and TS (+) (n = 17). Tregs sorted for CD4+CD25bright were co-cultured with autologous CD4+CD25− target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function.Results
Despite a lower frequency of CD4+ T cells in the TS (-) and TS (+) patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively), both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively). There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+CD25− T cells was significantly impaired in the TS (–) and TS (+) patients compared to controls (P = 0.003 and P = 0.041). Meanwhile, both the TS (–) and TS (+) groups had lower frequencies of naïve cells (P = 0.001 for both) but higher frequencies of effector memory cells (P = 0.004 and P = 0.002) than did the healthy control group.Conclusions
The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells. 相似文献17.
Background
IL-9 is a growth factor for T- and mast-cells that is secreted by human Th2 cells. We recently reported that IL-4+TGF-β directs mouse CD4+CD25−CD62L+ T cells to commit to inflammatory IL-9 producing CD4+ T cells.Methodology/Principal Findings
Here we show that human inducible regulatory T cells (iTregs) also express IL-9. IL-4+TGF-β induced higher levels of IL-9 expression in plate bound-anti-CD3 mAb (pbCD3)/soluble-anti-CD28 mAb (sCD28) activated human resting memory CD4+CD25−CD45RO+ T cells as compared to naïve CD4+CD25−CD45RA+ T cells. In addition, as compared to pbCD3/sCD28 plus TGF-β stimulation, IL-4+TGF-β stimulated memory CD4+CD25−CD45RO+ T cells expressed reduced FOXP3 protein. As analyzed by pre-amplification boosted single-cell real-time PCR, human CD4+IL-9+ T cells expressed GATA3 and RORC, but not IL-10, IL-13, IFNγ or IL-17A/F. Attempts to optimize IL-9 production by pbCD3/sCD28 and IL-4+TGF-β stimulated resting memory CD4+ T cells demonstrated that the addition of IL-1β, IL-12, and IL-21 further enhance IL-9 production.Conclusions/Significance
Taken together these data show both the differences and similarities between mouse and human CD4+IL9+ T cells and reaffirm the powerful influence of inflammatory cytokines to shape the response of activated CD4+ T cells to antigen. 相似文献18.
19.
Lentivirus infection activates CD4+ CD25+ T regulatory (Treg) cells. Activation of Treg cells may be due to direct virus infection or chronic antigenic stimulation. Herein we demonstrate that in vitro feline immunodeficiency virus (FIV) infection, but not UV-inactivated virus, activates Treg cells as measured by immunosuppressive function and upregulation of GARP, FoxP3, and membrane-bound transforming growth factor β (TGF-β). These data demonstrate for the first time that AIDS lentiviruses infect and activate Treg cells, potentially contributing to immune dysfunction. 相似文献