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Forkhead Box P3 (forkhead + box_p3)
Selected AbstractsNeuropilin-1 expression identifies a subset of regulatory T cells in human lymph nodes that is modulated by preoperative chemoradiation therapy in cervical cancerIMMUNOLOGY, Issue 1 2008Alessandra Battaglia Summary We examined the phenotype and function of CD4+ T cells expressing the semaphorin III receptor neuropilin-1 (Nrp1) in human lymph nodes and peripheral blood. In lymph nodes, Nrp1 identified a small regulatory CD4+ CD25high T-cell subpopulation (Nrp1+ Treg) that expressed higher levels of Forkhead box P3 (Foxp3) message and protein than Nrp1, Treg, and various molecular markers of activated Treg, i.e. CD45RO, human leucocyte antigen (HLA)-DR and glucocorticoid-induced tumour necrosis factor receptor (GITR). Similarly to conventional Treg, Nrp1+ Treg proliferated poorly in vitro, and exerted contact-dependent in vitro suppression of T-cell proliferation and cytokine secretion. However, Nrp1+ Treg were more efficient than Nrp1, Treg at inducing suppression. Nrp1 was also expressed on a small subpopulation of CD25int and CD25, CD4+ T cells that expressed more Foxp3, CD45RO, HLA-DR and GITR than their Nrp1, counterparts. In contrast, in peripheral blood Nrp1 identified a minor CD4+ T-cell subset that did not display the phenotypic features of Treg lacking Foxp3 expression and marginally expressing CD25. Hence, the function of Nrp1+ CD4+ T cells seemingly depends on their anatomical location. In a previous report, we proposed that Treg may curb the anti-tumour T-cell response in cervical cancer. We show here that Treg and Nrp1+ Treg levels dropped in the tumour-draining lymph nodes of patients with cervical cancer following preoperative chemoradiotherapy in a direct relationship with the reduction of tumour mass, suggesting that suppressor cell elimination facilitated the generation of T cells mediating the destruction of the neoplastic cells left behind after cytotoxic therapy. [source] Th17 cells: The emerging reciprocal partner of regulatory T cells in the liverJOURNAL OF DIGESTIVE DISEASES, Issue 3 2010Li ZHAO T helper cells that produce interleukin-17 (IL-17) (Th17 cells) have recently been identified as the third distinct subset of effector T cells, the differentiation of which depends on specific transcription nuclear factor retinoic acid-related orphan nuclear receptor-,t. Emerging data have suggested that Th17 cells play an important role in innate immunity, adaptive immunity and autoimmunity. Interestingly, there is a reciprocal relationship between Th17 cells and regulatory T cells (Treg), not only in development, but also in their effector function. Transforming growth factor (TGF)-, induces Treg-specific transcription factor Forkhead box P3(FOXP3), while the addition of IL-6 to TGF-, inhibits the generation of Treg cells and induces Th17 cells. It is proposed that the fine balance between Th17 and Treg cells is crucial for maintenance of immune homeostasis. In addition to IL-6, other factors such as retinoic acid, rapamycin, or cytokines (e.g., IL-2 and IL-27) could dictate the balance between Th17 and Treg cells. Since Treg cells play an important role in hepatic immunity with overregulation in chronic viral hepatitis and hepatic carcinoma, and inadequate inhibition in autoimmune liver diseases, graft rejection and acute liver failure, it is reasonable to assume that Th17 cells may play a reciprocal role in these diseases. Thus, future research on the Treg/Th17 balance may provide an opportunity to illustrate the pathogenesis of hepatic inflammation and to explore new therapeutic targets for immune-related liver diseases. [source] Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmissionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009Olivia C. Finney Abstract An important aspect of clinical immunity to malaria is the ability to down-regulate inflammatory responses, once parasitaemia is under control, in order to avoid immune-mediated pathology. The role of classical (CD4+CD25+CD127lo/,FOXP3+) Treg in this process, however, remains controversial. Thus, we have characterized the frequency, phenotype and function of Treg populations, over time, in healthy individuals in The Gambia. We observed that both the percentage and the absolute number of CD4+FOXP3+CD127lo/, T cells were higher among individuals living in a rural village with highly seasonal malaria transmission than among individuals living in an urban area where malaria rarely occurs. These CD4+FOXP3+CD127lo/, T cells exhibited an effector memory and apoptosis-prone phenotype and suppressed cytokine production in response to malaria antigen. Cells from individuals exposed to malaria expressed significantly higher levels of mRNA for forkhead box P3 and T-box 21 (T-BET) at the end of the malaria transmission season than at the end of the non-transmission season. Importantly, the ratio of T-BET to forkhead box P3 was remarkably consistent between populations and over time, indicating that in healthy individuals, a transient increase in Th1 responses during the malaria transmission season is balanced by a commensurate Treg response, ensuring that immune homeostasis is maintained. [source] A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis,,HEPATOLOGY, Issue 3 2010Silvia Ferri Immunotolerance is maintained by regulatory T cells (Tregs), including CD4+CD25hi, CD8+CD28,, ,,, and CD3+CD56+ [natural killer T (NKT)] cells. CD4+CD25hi cells are impaired in children with autoimmune hepatitis (AIH). Little is known about Tregs in adults with AIH. The aim of this study was to investigate the frequency and function of Treg subsets in adult patients with AIH during periods of active disease and remission. Forty-seven AIH patients (16 with active disease and 31 in remission) and 28 healthy controls were studied. Flow cytometry was used to evaluate surface markers and function-related intracellular molecules in ,,, CD8+CD28,, NKT, and CD4+CD25hi cells. CD4+CD25hi T cell function was determined by the ability to suppress proliferation and interferon gamma (IFN-,) production by CD4+CD25, target cells. Liver forkhead box P3,positive (FOXP3+) cells were sought by immunohistochemistry. In AIH patients, particularly during active disease, CD4+CD25hi T cells were fewer, expressed lower levels of FOXP3, and were less effective at inhibiting target cell proliferation versus healthy controls. Moreover, although the numbers of CD8+CD28, T cells were similar in AIH patients and healthy controls, NKT cells were numerically reduced, especially during active disease, and produced lower quantities of the immunoregulatory cytokine interleukin-4 versus controls. In contrast, ,, T cells in AIH patients were more numerous versus healthy controls and had an inverted V,1/V,2 ratio and higher IFN-, and granzyme B production; the latter was correlated to biochemical indices of liver damage. There were few FOXP3+ cells within the portal tract inflammatory infiltrate. Conclusion: Our data show that the defect in immunoregulation in adult AIH is complex, and ,, T cells are likely to be effectors of liver damage. (HEPATOLOGY 2010) [source] FOXP3 Expression in Human Kidney Transplant Biopsies Is Associated with Rejection and Time Post Transplant but Not with Favorable OutcomesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008S. Bunnag Expression of the transcription factor forkhead box P3 (FOXP3) in transplant biopsies is of interest due to its role in a population of regulatory T cells. We analyzed FOXP3 mRNA expression using RT-PCR in 83 renal transplant biopsies for cause in relationship to histopathology, clinical findings and expression of pathogenesis-based transcript sets assessed by microarrays. FOXP3 mRNA was higher in rejection (T-cell and antibody-mediated) than nonrejection. Surprisingly, some native kidney controls also expressed FOXP3 mRNA. Immunostaining for FOXP3 was consistent with RT-PCR, showing interstitial FOXP3+ lymphocytes, even in some native kidney controls. FOXP3 expression correlated with interstitial inflammation, tubulitis, interstitial fibrosis, tubular atrophy, C4d positivity, longer time posttransplant, younger donors, class II panel reactive antibody >20% and transcript sets reflecting inflammation and injury, but unlike these features was time dependent. In multivariate analysis, higher FOXP3 mRNA was independently associated with rejection, T-cell-associated transcripts, younger donor age and longer time posttransplant. FOXP3 expression did not correlate with favorable graft outcomes, even when the analysis was restricted to biopsies with rejection. Thus FOXP3 mRNA expression is a time-dependent feature of inflammatory infiltrates in renal tissue. We hypothesize that time-dependent entry of FOXP3-positive cells represents a mechanism for stabilizing inflammatory sites. [source] CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in miceARTHRITIS & RHEUMATISM, Issue 1 2009Paula Kolar Objective CD4+CD25+ regulatory T cells (known as Treg cells) suppress unwanted and autoreactive T cell responses. Treg cells express the costimulatory molecule CTLA-4 intracellularly, but the mechanisms by which Treg cells exploit CTLA-4 signaling remain unclear. The present study was undertaken to investigate the role of CTLA-4 in controlling the homeostasis and suppressive function of Treg cells. Methods Murine Treg cells were analyzed by flow cytometry for coexpression of CTLA-4 and typical Treg cell,expressed molecules, and the influence of CTLA-4 on T cell proliferation, suppression, and apoptosis was investigated by in vitro assays. To analyze the importance of CTLA-4 in Treg cell,mediated suppression in vivo, wild-type Treg cells were transferred into CTLA-4,deficient mice displaying lymphoproliferation, and survival was monitored over time. Results A strong correlation between expression of forkhead box P3 and ex vivo expression of CTLA-4 in Treg cells was observed. Inhibition of CTLA-4 signaling in Treg cells during in vitro stimulation increased cell cycling and led to enhanced activation-induced cell death (AICD), which was mediated by CD95/CD95 ligand,induced activation of caspases. Blockade of CTLA-4 signaling resulted in impairment of the suppressive capacity of Treg cells. Despite these effects, high amounts of Treg cells persisted in CTLA-4,deficient mice. Results of transfer experiments in CTLA-4,deficient mice showed that the mice had a significantly prolonged lifespan when CTLA-4,competent Treg cells were injected. Conclusion Expression of CTLA-4 on Treg cells serves to control T cell proliferation, to confer resistance against AICD, and to maintain the suppressive function of Treg cells. [source] Increased number and function of FoxP3 regulatory T cells during experimental arthritisARTHRITIS & RHEUMATISM, Issue 12 2008Kristen Monte Objective CD4+CD25+FoxP3+ regulatory T (Treg) cells are critical regulators of autoimmunity. Yet the number of Treg cells is paradoxically increased in rheumatoid arthritis (RA) patients, and Treg cells show variable activity in human studies. The objective of this study was to characterize the expansion and function of Treg cells during the initiation and progression of experimental arthritis. Methods To unequivocally identify Treg cells, we crossed FoxP3gfp mice with K/BxN mice to generate arthritic mice in which Treg cells express green fluorescence protein. We examined the expansion and function of Treg cells and effector T (Teff) cells during different stages of arthritis, using flow cytometry and cell proliferation analyses. Results In K/BxN mice, thymic selection of KRN T cells resulted in an enrichment of forkhead box P3 (FoxP3),positive Treg cells. Treg cell numbers increased during arthritis, with significant increases in spleens and draining lymph nodes, indicating selective tropism to sites of disease. In contrast to the in vitro unresponsiveness of Treg cells when cultured alone, substantial proportions of Treg cells proliferated in both nonarthritic and arthritic mice. However, they also underwent greater apoptosis, thereby maintaining equilibrium with Teff cells. Similarly, enhanced Treg cell,suppressive activity during arthritis was offset by greater resistance by their Teff cell counterparts and antigen-presenting cells. Conclusion In this well-established model of RA, the interplay of Teff cells and Treg cells in K/BxN mice recapitulated many features of the human disease. We demonstrated an ordered expansion of Treg cells during arthritis and dynamic changes in Treg cell and Teff cell functions. By elucidating factors that govern Treg cell and Teff cell development in K/BxNgfp mice, we will gain insight into the pathophysiology of and develop novel therapeutics for human RA. [source] Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-,,producing antigen-presenting cellsARTHRITIS & RHEUMATISM, Issue 3 2008Bing Yan Objective To explore whether there are extrinsic factors that impair the suppressive function of CD4+,CD25+ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE). Methods We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4+,CD25+,FoxP3+ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-, (IFN,) in supernatants from the function assays were determined with an IFN-stimulated response element,luciferase reporter assay. Results The percentage of CD4+,CD25+, FoxP3+ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean ± SEM 9.11 ± 0.73% versus 4.78 ± 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4+,CD25+ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4+,CD25+ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFN, derived from SLE patient APCs. Conclusion We suggest that blockade of Treg cell,mediated suppression by IFN,-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease. [source] Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remissionARTHRITIS & RHEUMATISM, Issue 6 2007Wayel H. Abdulahad Objective Accumulating data support the role of regulatory T cells, a subset of CD4+ T cells that expresses CD25high and the transcription factor forkhead box P3 (FoxP3), in controlling and preventing autoimmunity. In Wegener's granulomatosis (WG), an autoimmune vasculitis, up-regulation of CD25 on circulating CD4+ T cells has been observed, even in patients in remission. The objective of this study was to test whether the frequency and/or function of Treg cells from WG patients in remission are disturbed. Methods Peripheral blood mononuclear cells were freshly isolated from 52 WG patients in remission and from 27 age- and sex-matched healthy control subjects. The proportion of circulating Treg cells was assessed by flow cytometry using CD4, CD25, FoxP3, and CD45RO markers. Anergy and suppressive function of CD25high,CD4+ T cells were determined using polyclonal stimulants and coculture assay in 10 WG patients in remission and in 10 age- and sex-matched healthy controls. Results In WG patients, a significant increase was observed in the percentage of circulating CD25high,CD4+ and CD25low,CD4+ T cells, whereas CD25,,CD4+ T cells were decreased, as compared with healthy controls. Among circulating CD4+ T cells, an expanded percentage of Treg cells (CD25high,FoxP3+) with memory phenotype was present in WG patients. However, when the suppressive function of CD25high,CD4+ T cells was tested, CD25high,CD4+ T cells from WG patients showed diminished or absent suppression of responder T cell proliferation. The impaired suppression was not due to responder cell resistance (as shown by crisscross experiments with T cells from healthy controls) or altered survival of Treg cells. Conclusion These data indicate that WG patients in remission have an expanded proportion of Treg cells that are functionally defective. This observation may be relevant to the development and relapsing course of this autoimmune vasculitis. [source] Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune toleranceCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010K. J. Lee Summary Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-, and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (Treg) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-, and IDO production and the proliferation of Tregs using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-, in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth. [source] Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitisCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2009M. Okano Summary Allergic rhinitis is a common airway disease characterized by hypersensitivity, exudation, hypersecretion, inflammatory cell infiltration and remodelling. Intranasal glucocorticosteroids are the most effective drugs for controlling the inflammation caused by allergic rhinitis. Glucocorticosteroids exert anti-inflammatory effects through at least two pathways: the transactivation pathway and the transrepression pathway. Glucocorticosteroids also exert regulatory functions by inducing regulatory cytokines and forkhead box P3 (FoxP3+) regulatory T cells. Evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H1 receptor antagonists, intranasal glucocorticosteroids can improve impaired performance symptoms, such as daytime sleepiness, associated with allergic rhinitis. Recent studies suggest that intranasal glucocorticosteroids might also be useful for the prophylactic treatment of pollinosis; this possibility is supported by the molecular mechanism of the anti-inflammatory action of glucocorticosteroids. These findings suggest that intranasal glucocorticosteroids might be positioned as first-line drugs for the treatment of both perennial and seasonal allergic rhinitis. [source] Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasiaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2007J. Visser Summary Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-,/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-, T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. [source] Dynamic changes in CD4+ CD25+ high T cell apoptosis after the diagnosis of type 1 diabetesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2007S. Glisic-Milosavljevic Summary Because type 1 diabetes (T1D) is a chronic, autoimmune, T cell-mediated disease, interventions affecting T cells are expected to modulate the immune cascade and lead to disease remission. We propose that increased CD4+ CD25+high T cell apoptosis, a trait we discovered in recent-onset T1D subjects, reflects T1D partial remission within the first 6 months after diagnosis. Apoptosis of forkhead box P3 (FoxP3)+ CD4+ CD25+high T cells, in addition to total daily doses of insulin (TDD), blood glucose, HbA1c and age, were measured in 45 subjects with T1D at various times after diagnosis. Sixteen healthy control subjects were also recruited to the study. Higher CD4+ CD25+high T cell apoptosis levels were detected within the first 6 months of diagnosis (odds ratio = 1·39, P = 0·009), after adjustment for age, TDD and HbA1c. A proportional hazards model confirmed that the decline of apoptosis after diagnosis of T1D was related significantly to survival time (hazards ratio = 1·08, P = 0·014), with TDD and age also contributing to survival. During this time there was an inverse relationship between CD4+ CD25+high T cell apoptosis with TDD (r = ,0·39, P = 0·008). The CD4+ CD25+high T cell apoptosis levels decline significantly after the first 6 months from diagnosis of T1D and may help in the close monitoring of autoimmunity. In parallel, there is an increase in TDD during this time. We also propose that CD4+ CD25+high T cell apoptosis assay can be used to gauge the efficacy of the several immune tolerance induction protocols, now under way. [source] The role of CD4+CD25+ T cells in autoantibody production in murine lupusCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006W.-T. Hsu Summary Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by the loss of tolerance to self-antigen. Because it is currently not known if regulatory T (Treg) cells are involved in the pathogenesis, we determined the frequency of CD4+CD25+ T cells and assayed the related gene expression levels in CD4+CD25+ T cells isolated from both lupus mice (NZB/NZW F1) and normal control mice (DBA2/NZW F1). The results showed that the frequency of CD4+CD25+ T cells in lupus mice was lower than that of normal mice. Except for the high expression level of interleukin (IL)-10 mRNA, CD4+CD25+ T cells from lupus mice expressed normal forkhead box P3 (Foxp3) and transforming growth factor (TGF)-, mRNA, and exerted suppressive functions. Furthermore, we depleted CD25+ Treg cells of non-autoimmune mice with anti-CD25 antibody and broke their tolerance with apoptotic cell-pulsed dendritic cells for the follow-up of autoantibody levels. The mice in the CD25+ cell-depleted group had higher titres of anti-double-strand/single-strand DNA antibodies than those of the isotype control antibody-treated group. These findings indicated that CD4+CD25+ T cells might be involved in the regulatory mechanism of autoantibody production. [source] Interstitial Foxp3-positive T cells may predict renal survival in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritisCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2010Junko Yoshimura Summary 1. Regulatory T cells (Treg) and cytotoxic T cells (CTL) are involved in various immune diseases. However, the prognostic impact of Treg and CTL in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) is not well known. Therefore, in the present study, we examined the relationship between expression of forkhead box P3 (Foxp3) and T cell intracytoplasmic antigen (TIA)-1, Treg and CTL markers and renal survival in patients with MPO-ANCA-GN. 2. Forty patients with MPO-ANCA-GN and 10 patients with minimal change nephrotic syndrome (MCNS) underwent physical examination, determination of blood chemistry and renal biopsy. Immunohistochemical staining for Foxp3 and TIA-1 was performed on paraffin-embedded renal sections. 3. Although almost all patients received standard immunosuppressive treatment for 6 months, seven MPO-ANCA-GN patients needed maintenance haemodialysis (HD), whereas 33 patients did not (non-HD). Both Foxp3- and TIA-1-positive cells were detected in the interstitium and glomeruli of MPO-ANCA-GN patients, whereas they were rarely detected in patients with MCNS. The total crescent rate was significantly higher in the HD group than in the non-HD group (35.9 ± 3.5 vs 65.8 ± 7.4, respectively). In the interstitium, the age-adjusted Foxp3/TIA-1 ratio was significantly higher in the non-HD group than in the HD group (0.016 ± 0.016 vs 0.004 ± 0.008, respectively; P < 0.05). The Foxp3/TIA-1 ratio, but not the Foxp3/CD3 ratio, remained significantly higher in the non-HD group than in the HD group even after adjustment for crescent rate. Age- and total crescent rate-adjusted renal survival rates were higher in patients with a Foxp3/TIA-1 ratio , 0.06 than in patients with a Foxp3/TIA-1 ratio < 0.06 (P = 0.02). 4. The results of the present study suggest that Treg could play a protective role against MPO-ANCA-GN and that a decreased Foxp3/TIA-1 ratio in interstitial areas may predict future renal failure in patients with MPO-ANCA-GN. [source] | ||||||||||