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Factor Foxp3 (factor + foxp3)
Kinds of Factor Foxp3 Selected AbstractsA Possible Role of CD4+CD25+ T Cells as Well as Transcription Factor Foxp3 in the Dysregulation of Allergic RhinitisTHE LARYNGOSCOPE, Issue 5 2007Geng Xu MD Abstract Background: Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4+CD25+ T cells account for approximately 5% to 10% peripheral CD4+ T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4+CD25+ T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4+CD25+ T cells as well as Foxp3 in the pathogenesis of AR. Methods: Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4+CD25+ T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-, (IFN-,) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin. Results: The numbers of Foxp3+ cells was 129.5 ± 35.6 and 44.2 ± 20.5 cells/mm2 in nasal mucosa of two groups (P < .05). There were less Foxp3+ lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4+CD25+ population in PBMCs of two groups were 1.99 ± 0.95% and 3.55 ± 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3+CD4+ CD25+ population (1.81 ± 0.77 vs 3.37 ± 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 ± 2.64 vs 11.72 ± 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-, were 182.72 ± 85.11 pg/mL and 348.94 ± 151.88 pg/mL in PBMCs with AR, while those were 90.6 ± 61.5 pg/mL and 155.64 ± 68.33 pg/mL in controls (P < .05). Conclusion: Our results indicate that CD4+ CD25+ regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4+CD25+ T cells have the potential to be new therapeutic targets for the treatment of AR. [source] Clinical outcome and IL-17, IL-23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-II 2010Kaisa Nieminen Nieminen K, Valovirta E, Savolainen J. Clinical outcome and IL-17, IL-23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapy. Pediatr Allergy Immunol 2010: 21: e174,e184. © 2009 John Wiley & Sons A/S Induction of allergen-specific, tolerogenic, IL-10 and/or TGF-,-producing T-regulatory (Treg) cells that express transcription factor FOXP3 is considered as one of the key mechanisms of allergen-specific immunotherapy. However, little is known of the induction of FOXP3 expression in children during sublingual immunotherapy (SLIT). Recently, also, a novel subgroup of T-helper (Th) cells, the Th17 cells, secreting predominantly IL-17 (IL-17A), was identified. The expressions of IL-17 or the Th17-regulating cytokines IL-23 and IL-27 during SLIT are currently completely unexplored. This randomized, placebo-controlled dose-response study was performed to analyze the effects of SLIT on FOXP3, IL-17, IL-23, and IL-27 expressions in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis and their associations with clinical outcome. Thirty children were included: ten received SLIT with a glycerinated mixture of birch, hazel and alder with a cumulative weekly dose of 24,000 SQ-U, 10 with dose 200,000 SQ-U/wk, and ten received placebo. Cytokine and FOXP3 mRNA expressions in allergen-, purified protein derivative-stimulated and non-stimulated PBMC were determined at 0, 1 and 2 yr of SLIT by real-time RT-PCR (TaqMan®). Symptoms and medications were recorded using diary cards. Allergen-induced IL-17 mRNA expression was significantly increased in the study subjects with elevated combined Symptom Medication Score (SMS) after 2 yr. There was also a significant positive correlation between the allergen-induced IL-17 and SMS in whole study group (r = 0.38, p = 0.039) and especially the 200,000 SQ-U dose-treated group (r = 0.74, p = 0.027) at 2 yr. Allergen-induced FOXP3 mRNA expression was significantly increased in the 200,000 SQ-U dose-treated children after two study years as compared with baseline (p = 0.016) and placebo-treated children (p = 0.028). The changes in FOXP3 mRNA expression positively correlated with IL-10 and TGF-, mRNAs during SLIT in whole study population. Increased allergen-induced IL-17 responses during SLIT are associated with elevated SMS. Increased tolerogenic, allergen-specific Treg responses are also observed in children during SLIT. [source] Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2006Gennadiy Zelinskyy Abstract Cytolytic CD8+ T cells are critical for the control of acute Friend virus (FV) infection yet they fail to completely eliminate the virus during chronic infection because they are functionally impaired by regulatory T cells (Treg). We performed a kinetic analysis of T cell responses during FV infection to determine when dysfunction of CD8+ T cells and suppressive activity of CD4+ regulatory T cells develops. At 1,week post infection, virus-specific CD8+ T cells with effector phenotype and cytolytic potential expanded. Peak expansion was found at 12,days post infection, correlating with peak viral loads. After 2,weeks when viral loads dropped, numbers of activated CD8+ T cells started to decline. However, a population of virus-specific CD8+ T cells with effector phenotype was still detectable subsequently, but these cells had lost their ability to produce granzymes and to degranulate cytotoxic molecules. Contemporaneous with the development of CD8+ T cell dysfunction, different CD4+ T cell populations expressing cell surface markers for Treg and the Treg-associated transcription factor Foxp3 expanded. Transfer as well as depletion experiments indicated that regulatory CD4+ cells developed during the second week of FV infection and subsequently suppressed CD8+ T cell functions, which was associated with impaired virus clearance. [source] A Possible Role of CD4+CD25+ T Cells as Well as Transcription Factor Foxp3 in the Dysregulation of Allergic RhinitisTHE LARYNGOSCOPE, Issue 5 2007Geng Xu MD Abstract Background: Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4+CD25+ T cells account for approximately 5% to 10% peripheral CD4+ T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4+CD25+ T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4+CD25+ T cells as well as Foxp3 in the pathogenesis of AR. Methods: Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4+CD25+ T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-, (IFN-,) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin. Results: The numbers of Foxp3+ cells was 129.5 ± 35.6 and 44.2 ± 20.5 cells/mm2 in nasal mucosa of two groups (P < .05). There were less Foxp3+ lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4+CD25+ population in PBMCs of two groups were 1.99 ± 0.95% and 3.55 ± 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3+CD4+ CD25+ population (1.81 ± 0.77 vs 3.37 ± 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 ± 2.64 vs 11.72 ± 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-, were 182.72 ± 85.11 pg/mL and 348.94 ± 151.88 pg/mL in PBMCs with AR, while those were 90.6 ± 61.5 pg/mL and 155.64 ± 68.33 pg/mL in controls (P < .05). Conclusion: Our results indicate that CD4+ CD25+ regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4+CD25+ T cells have the potential to be new therapeutic targets for the treatment of AR. [source] Vaccination with selected synovial T cells in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 2 2007Guangjie Chen Objective This pilot clinical study was undertaken to investigate the role of T cell vaccination in the induction of regulatory immune responses in patients with rheumatoid arthritis (RA). Methods Autologous synovial T cells were selected for pathologic relevance, rendered inactive by irradiation, and used for vaccination. Fifteen patients received T cell vaccination via 6 subcutaneous inoculations over a period of 12 months. Results T cell vaccination led to induction of CD4+ Tregs and CD8+ cytotoxic T cells specific for T cell vaccine. There was selective expansion of CD4+,V,2+ Tregs that produced interleukin-10 (IL-10) and expressed a high level of transcription factor Foxp3, which coincided with depletion of overexpressed BV14+ T cells in treated patients. CD4+ IL-10,secreting Tregs induced by T cell vaccination were found to react specifically with peptides derived from IL-2 receptor ,-chain. The expression level of Foxp3 in CD4+ T cells and increased inhibitory activity of CD4+,CD25+ Tregs were significantly elevated following T cell vaccination. The observed regulatory immune responses collectively correlated with clinical improvement in treated patients. In an intent-to-treat analysis, a substantial response, defined as meeting the American College of Rheumatology 50% improvement criteria, was shown in 10 of the 15 patients (66.7%) and was accompanied by a marked improvement in RA-related laboratory parameters. Conclusion These findings suggest that T cell vaccination induces regulatory immune responses that are associated with improved clinical and laboratory variables in RA patients. [source] Seasonal changes in suppressive capacity of CD4+ CD25+ T cells from patients with hayfever are allergen-specific and may result in part from expansion of effector T cells among the CD25+ populationCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2009A. E. Anderson Summary Background Suppression of allergen-stimulated peripheral blood CD4+ CD25, effector T cells by CD4+ CD25+ regulatory T cells obtained from subjects with allergic rhinoconjunctivitis is reduced during the pollen season when compared with out of season. Objective We examined possible explanations for this effect of seasonal pollen exposure on suppression of allergen responses. Methods CD4+ CD25, and CD4+ CD25+ T cells were isolated from blood obtained from 44 volunteers with allergic rhinoconjunctivitis during and out of the UK grass pollen season. Co-cultures were performed with grass pollen extract and house dust mite (HDM) to examine allergen specificity. The frequency of IL-5 and IL-10 producing cells was determined by ELISPOT and the expression of T cell activation markers and the CD25+ regulatory T cell-associated transcription factor Foxp3 were examined. Lactic acid stripping of IgE was used to determine IgE dependence of T cell responses. Results The seasonal reduction in suppression by CD4+ CD25+ T cells was confirmed and was shown to be allergen specific because suppression of HDM-stimulated cultures was not affected significantly. The CD4+ CD25+ population contained IL-5 and IL-10 producing cells but increases in their frequencies with seasonal pollen exposure were not significant. Both activation marker and Foxp3 expression increased during the pollen season. IgE stripping reduced CD4+ and CD4+ CD25, T cell responses to allergen, but had no effect on suppression by CD4+ CD25+ T cells. Conclusion The seasonal reduction in suppression of grass pollen-stimulated effector T cells by CD4+ CD25+ T cells is allergen specific and cannot be explained by increased IgE-facilitated allergen presentation. We suggest that changes in the proportion of effector to regulatory T cells among the CD25+ population isolated may partially explain these findings, and that trafficking to the site of allergic disease may reduce allergen-specific regulatory T cell numbers in peripheral blood. [source] | ||||||||||