Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ (”naive” helper T cells, suppressor-inducer), CD45RA+CD8+ (”naive” suppressor T cells, suppressor-effector), CD45RO+CD4+ (”memory” helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-γ, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18±0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05±0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2±0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82±0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85±0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5±0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS. Received: 3 November 1998 / Revised: 1 September 1999 / Accepted: 8 September 1999     

ATG induction therapy: long-term effects on Th1 but not on Th2 responses

Antithymocyte globulin (ATG) induction therapy is associated with an increased long-term risk of infection- and cancer-related death. To analyze long-term effects of ATG induction on lymphocyte function, we prospectively assessed CD4 helper function, B-cell/monocyte and cytokine responses in 84 renal transplant recipients (ATG, n = 44) up to 1 year post-transplant. A PWM-driven allogeneic coculture system was used to assess helper function of CD4+ T cells and T-cell-dependent B-cell responses. SAC I was used for T-cell-independent stimulation of B-cell cultures. In vitro cytokine secretion and serum soluble CD30 (sCD30) were determined by enzyme-linked immunosorbent assay (ELISA). ATG induced a persistent decrease of peripheral blood lymphocyte counts compared with non-ATG treatment because of a predominant decrease of CD4+ T cells (4 months, 1 year; P < 0.0005) which was associated with a decreased CD28 expression (1 year, P = 0.02) and CD4 cell interleukin 2 (IL-2) response (4 months, P < 0.0005). However, Th2 responses (CD4 help, CD4 cell IL-4 and IL-10 responses, sCD30), which proved to be predictive of graft outcome, were not affected, and neither was the secretion of the lymphoma growth factors IL-6 and IL-10 by B cells and monocytes. Our data show that ATG induction therapy in immunological high-risk patients induces a profound long-term decrease in cell counts and Th1 but not Th2 responses of CD4+ T cells which may explain long-term effects on infection and post-transplant lymphoproliferative disease (PTLD) incidence because of inadequate T-cell control.     

An alternate mechanism of glucocorticoid anti-proliferative effect: promotion of a Th2 cytokine-secreting profile

Glucocorticoids (GCs) are used as immunosuppressive and anti-inflammatory agents in organ transplantation and in treating autoimmune diseases and inflammatory disorders and they exert their effects by several mechanisms, the most significant of which is inhibition of cytokine production and action. Recent reports suggested that GCs inhibit cytokine expression indirectly through promotion of a T helper cell type 2 (Th2) cytokine-secreting profile, thereby resulting in preferential blockade of pro-inflammatory monokine and T helper cell type 1 (Th1) cytokine expression. The target of GCs appeared to be monocytes macrophages, whereby altered regulation of interleukin (IL)-1/IL-1 receptor antagonist (IL-1ra), coupled with profound blockade of IL-12 synthesis and inhibition of interferon (IFN)-gamma-induced major histocompatibility complex (MHC) class II expression, lead to a preferential cognate stimulation of Th2 cells at the expense of Th1 cells. It is possible that this may have involved the expansion of a Th2-cell pool or, in addition, frank stimulation of uncommitted naive CD4 + T cells toward the Th2 lineage. In addition, GCs may have blocked Th1 cytokine expression, thereby inhibiting ongoing Th1 cytokine secretion, and consequently provided for the unimpeded production of Th2 cytokines. Collectively, this indicates that, in exerting their anti-proliferative effects, GCs act indirectly by altering Th1/Th2 cytokine balance, blocking the (pro-inflammatory) Th1 program and favoring the (anti-inflammatory) Th2 program.     

Th2 subset dominance among peripheral blood T lymphocytes in patients with digestive cancers

BACKGROUND: Two types of helper T cells (Th), which are categorized as Th1 and Th2 on the basis of cytokine production, have been reported. Th1 cells produce interleukin (IL)-2 and interferon (IFN)-gamma, while Th2 cells secrete IL-4, IL-6, and IL-10. We assessed the intracellular cytokine profiles of CD3/CD4 positive lymphocytes (CD4+ T-cells) in peripheral blood in patients with digestive cancers. METHODS: Peripheral blood samples were collected from 50 patients with digestive cancers and 35 healthy volunteers. The proportions of CD4+ T-cells producing intracellular cytokines were determined using flow cytometry. RESULTS: The percentages (mean +/- SD) of CD4+ T-cells producing IL-4, IL-6, and IL-10 in the cancer group (73.9% +/- 13.0%, 73.0% +/- 16.6%, and 58.0% +/- 21.0%, respectively) were significantly higher than in the healthy group (37.4% +/- 12.4%, 37.8% +/- 13.5%, and 34.0% +/- 14.1%, respectively; P <0.01). Proportions of CD4+ T-cells producing IL-4, IL-6, and IL-10 in 10 patients undergoing curative resection had decreased significantly 1 month after surgery (P <0.01). No significant difference was noted between groups in the percentages of CD4+ T-cells producing IFN-gamma. CONCLUSIONS: Th2-dominant status develops in cancer patients. Such lymphocyte evaluations could find applications in diagnosis and therapeutic monitoring of cancer patients.     

Use of intracellular cytokine staining and bacterial superantigen to document suppression of the adaptive immune system in injured patients

OBJECTIVE: To determine the percentages of major T lymphocyte subsets in the circulating peripheral blood mononuclear cell population in patients with major traumatic injury at early and late time points and to determine the expression of coreceptors and cytokine production by these T cell subsets. SUMMARY BACKGROUND DATA: Prior studies suggest that serious injury in humans suppresses the adaptive immune system as revealed by diminished proliferation and altered cytokine production in response to polyclonal T cell activation. However, the contribution of individual cell types to this immune dysfunction has not been well characterized. METHODS: The percentage of circulating CD4+ and CD8+ T cells and the relative density of CD4 and CD8 coreceptor expression was determined by flow cytometry in 17 consecutive trauma patients (injury severity score > 20) within 24 hours of injury and at day 7. Intracellular expression of the cytokines interleukin 2 (IL-2), interferon gamma (IFNgamma), IL-4, and IL-10 were also studied after stimulation with bacterial superantigen (SEB). Patients were compared with age- and sex-matched controls and to themselves for differences between early and late cytokine expression. RESULTS: The percentage of circulating CD4+ and CD8+ T cells was decreased versus controls at day 1 and further decreased by day 7 following injury. CD4 and CD8 cell surface expression was also decreased at days 1 and 7. CD4+ T cells in injured patients responded to SEB activation with decreased expression of IFNgamma and IL-2 on day 1 versus controls (P < 0.05) and of all 4 cytokines by day 7 (P < 0.05), while CD8+ T cells showed diminished expression of IFNgamma and IL-2 only at both time points. When day 1 and day 7 cytokine expression results were compared in the same patients, CD4+ T cells showed diminished expression of IFNgamma, IL-2, and IL-4 by day 7 (P < 0.05), but maintained expression of IL-10. CD8 T cells showed diminished expression of IFNgamma only. CONCLUSIONS: Severe injury induces a loss of circulating CD4+ and CD8+ T lymphocytes and diminished coreceptor expression by these cells. Both T cell subsets show progressive loss of immunostimulatory cytokine production with maintenance of potentially suppressive IL-10 production. These events may have negative consequences for host defense.     

Th2 cytokine profile in infants predisposes to improved graft acceptance after liver transplantation

BACKGROUND: The T helper cell type 1 (Th1) cytokines interleukin (IL)-2 and interferon (IFN)-gamma are mediators of acute graft rejection after liver transplantation and Th2 cytokines, such as IL-4 and IL-10, may have a protective role and correlate with graft acceptance. To test the hypothesis that infants aged <1 year have an immunological advantage with regard to graft acceptance because of a partially immature immune system with a physiological balance toward a Th2 cytokine profile, we conducted the present study. METHODS: We compared the T helper serum cytokine profiles in 105 infants and children after liver transplantation with or without acute graft rejection and analyzed the normal age-distributed concentrations of T helper cytokines in 51 healthy controls. RESULTS: The incidence of acute graft rejection was as follows: 0 to 12 months, 26.8%; 1 to 3 years, 40.0%; and >3 years, 71.8%. There was a significantly lower incidence of acute rejection in infants 0 to 12 months of age compared with children >1 year (11/41 vs. 38/64; P=0.001). In healthy infants, significant increasing Th1 cytokine concentrations and decreasing Th2 cytokine concentrations were found with increasing age. Patients with acute rejection had significantly higher values of Th1 cytokines compared with nonrejecting subjects, who had significantly higher concentrations of Th2 cytokines. A longitudinal analysis of serum cytokines from patients showed that changes of the cytokine patterns in the follow-up did not differ significantly from preoperative values, except in the 4 weeks posttransplant. CONCLUSIONS: We conclude from the data that the physiological balance toward a Th2 cytokine profile of infants in the first months of life predisposes to improved graft acceptance. Transplantation of children with biliary atresia as early as possible, avoiding Th1 stimulation by recurrent infections and vaccinations, may have a positive impact on overall tolerance.     

T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients.

BACKGROUND: Patients on chronic intermittent haemodialysis (HD) show an impaired cellular and humoral immune response that clinically appears with frequent infectious complications and low vaccination responses. This immune defect strongly correlates with reduced in vitro proliferative responses of T cells. The defect is localized in antigen presenting cells, which show a decreased co-stimulatory activity. Furthermore, the impaired immune response correlates with an increased production of pro-inflammatory cytokines. In response to primary activation, CD4 positive T helper (Th) cells mainly differentiate into either Th1 or Th2 cells. Th1 cells support cell mediated immunity whereas Th2 cells enhance humoral immune responses. Since both types of responses mutually inhibit each other, the impaired humoral immune response seen in HD patients could either be due to a reduced number of Th2 cells or to a predominant Th1 response. METHODS: We analysed the Th cell profile in HD patients using flow cytometry. Monocytic cytokine expression was analysed using both flow cytometry and enzyme linked immunoadsorbant assays. RESULTS: Our data demonstrate that the cytokine differentiation profile in circulating T cells from HD patients is dysregulated and characterized by an increase in Th1 cells, but a normal amount of Th2 cells. Moreover, the skewed helper cell responses correlate with a higher percentage of monocytes capable of secreting the Th1 promoting cytokine interleukin 12 (IL-12). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of impaired cellular immune functions in dialysis patients and, in particular, the decreased antibody production after vaccination. They provide a link between overproduction of pro-inflammatory cytokines (IL-12) and imbalanced T-cell activation.     

T cell cytokine profiles in childhood asthma

BACKGROUND: An imbalance of T cell subsets in asthma with a predominance of Th2 type cells has been proposed. The aim of this study was simultaneously to detect surface markers and intracellular production of cytokines in T cells from the airways of children with and without asthma. METHODS: Bronchoalveolar lavage (BAL) fluid was obtained by wedging a suction catheter into the distal airway immediately before elective surgery. Cells were stimulated with phorbol 12-myristrate 13-acetate (PMA) and ionomycin and intracytoplasmic cytokine retention was achieved using monensin. The cells were stained with the relevant antibodies and analysed by flow cytometry. RESULTS: No statistical difference was observed between children with atopic asthma, atopic non-asthmatic subjects, and normal controls in the percentage of CD3+ cells producing interleukin (IL)-2 or IL-4. Interferon (IFN)gamma+ T cells were, however, present in a much higher percentage than either IL-2 or IL-4 positive cells. The percentage of IFNgamma+ T cells was significantly increased in subjects with atopic asthma (median 71.3%, interquartile range (IQR) 65.1-82.2, n=13) compared with both atopic non-asthmatic subjects (51.9%, IQR 37.2-70.3, n=12), p<0.05 and normal controls (58.1%, IQR 36.1-66.1, n=23), p<0.01. CONCLUSIONS: These findings indicate that IFNgamma producing T cells are more abundant in the airways of children with atopic asthma than in atopic non-asthmatic subjects and controls. The proinflammatory activities of IFNgamma may play an important role in the pathogenesis of childhood asthma and may suggest that asthma is not simply a Th2 driven response.     

Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity

OBJECTIVES: We recently reported increased CD4 CD25 T regulatory (Treg) activity after burn injury in mice. This study sought to determine if Tregs mediate the reduction in TH1-type immunity after serious injury in man and if Treg function is altered by injury. METHODS: Peripheral blood was withdrawn from 19 consenting adult patients (35.1 +/- 16.3 years of age) with Injury Severity Scores (ISS) 36.6 +/- 13.9 on days 1 and 7 after trauma and from 5 healthy individuals. CD4 T cells were purified and sorted into Treg (CD25(high)) and Treg-depleted populations. After activation of cells with anti-CD3/CD28 antibody, production of the TH1-type cytokine IFNgamma, TH2-type cytokines (IL-4 and IL-5), and the inhibitory cytokine IL-10 was measured using cytometric bead arrays. Treg activity was measured by in vitro suppression of autologous CD4 T cell proliferation. RESULTS: All patients survived, 9 (47%) developed infection postinjury. IFNgamma production by patient CD4 T cells was decreased on day 1 and day 7, when compared with healthy controls. However, when Tregs were depleted from the CD4 T cells, the IFNgamma production increased to control levels. Tregs were the chief source of IL-4 and IL-5 as well as IL-10. Treg suppression of T cell proliferation increased significantly from day 1 to day 7 after injury. CONCLUSIONS: We demonstrate for the first time that human Tregs are increased in potency after severe injury. Most significantly, Tregs are important mediators of the suppression of T cell activation and the reduction in TH1 cytokine production found after injury.     

Superior 3-year kidney graft function in patients with impaired pretransplant Th2 responses

Abstract In a prospective study of 80 patients, we investigated the association of kidney graft rejection with pretransplant CD4 helpersuppressor function, B cell responses, and in vitro cytokine secretion. A pokeweed mitogen-driven allogeneic coculture system was used to assess CD4 helper/suppressor function and T cell-dependent B cell responses. SAC I was used for T celland monocyte-independent stimulation of B cell cultures. B cell differentiation was assessed in a reverse hemolytic plaque assay. ELISAs were used to determine in vitro cytokine secretion. None of the 12 patients with pretransplant CD4 helper defects (<10% helper activity) had acute rejection episodes in contrast to 32 of 68 (47%) patients with normal pretransplant CD4 helper function ( P = 0.001). Patients with pretransplant CD4 helper defects exhibited better 3-year graft function than patients without CD4 helper defects (serum creatinine of functioning grafts: 1.2 ± 0.1 mg/dl compared to 1.7 ± 0.1 mg/dl, P < 0.05). Low pretransplant IL-10 responses (<100 pg/ml; 14/80 patients) were significantly associated with a low incidence of acute rejection episodes ( P < 0.01) and good 3- year graft function ( P < 0.05). These data show that impaired pretransplant Th2 responses-CD4 help and IL-10 responses-predict a low risk of kidney graft rejection and good 3-year graft function, whereas Th1 (IL-2, IFN-γ) and B cell/monocyte responses are not of predictive value.     

Naive CD4+ cells from cord blood can generate competent Th effector cells

BACKGROUND: Umbilical cord blood (UCB) cells have been increasingly used as a source of hematopoietic stem cells for allogeneic transplantation. Previous reports suggest that the low risk of graft-versus-host disease in patients that received cord blood cells seems related to the distinctive nature of cord blood T cells. METHODS: To analyze the maturation of CD4+CD45RA+ cord blood cells, we performed an in vitro differentiation assay to compare the generation of Th effector cells strictly from UCB and adult peripheral blood (APB) CD4+CD45RA+ cells. RESULTS: During the maturation into effector cells, UCB and APB cells acquired a comparable activation level determined by the expression pattern of CD69, CD40L, OX40 and CD62L as well as PD1 and CTLA-4 molecules. Moreover, the expression of CD45RO isoform was induced in most activated effector cells from both UCB and APB. OKT3-restimulated effector cells generated from naive UCB expressed higher levels of CD25 coinciding with the secretion of higher amounts of IL-2. Effector cells from both origins consisted of heterogeneous populations with similar frequencies of Th1 and Th2 cytokine producing cells, secreting equivalent levels of IL-4, IL-5 and IFNgamma. Although, higher levels of IL-10 were detected in the cytokine mRNA profile and in the supernatants of OKT3-restimulated UCB effector cells, blocking endogenous IL-10 with anti-IL-10 mAbs enhanced significantly the proliferative response of UCB as well as APB effector cells (P < 0.05). CONCLUSIONS: These results indicated that Th effector cells generated from naive UCB cells were intrinsically as competent as naive APB to respond to TCR-mediated stimulation. In addition, UCB effector cells produced higher IL-10 but its inhibitory effect on proliferation may be partially compensated by the higher production of IL-2 and enhanced expression of CD25.     

共刺激后淋巴细胞产生Th1/Th2细胞因子的变化及免疫抑制剂的影响

目的 探讨CD28、CD40通路共刺激后淋巴细胞产生Th1(IL-2、IFN-γ、IL-12)及Th2细胞因子(IL-4、IL-10)的变化及免疫抑制剂环孢素(CsA)、雷帕霉素(RPM)及霉酚酸(MPA)对共刺激通路激活后淋巴细胞产生Th1及Th2细胞因子的影响.方法采用单克隆抗体(mAb)与淋巴细胞表面CD3、CD28及CD40L分子结合产生相应刺激信号,单刺激及共刺激组分为:a组,CD3 mAb单刺激;b组,CD3 mAb加CD28 mAb共刺激;c组,CD3 mAb加CD28 mAb加CD40 L mAb共刺激;d组,CD3 mAb加CD28 mAb加CTLA4 mAb共刺激.各mAb的终浓度均为100 ng/ml.干预组分别将终浓度为300 ng/ml的CsA、RPM、MPA加入上述4组.ELISA法测定上述细胞培养上清中的细胞因子值.结果 a、b、c 3组IFN-γ分别为(248.91±11.20)、(555.08±24.42)、(548.19±33.06)ng/ml,IL-2分别为(29.48±8.61)、(1100.82±99.29)、(842.23±29.31)ng/ml,IL-4分别为(32.29±6.76)、(116.02±15.03)、(147.28±18.07)ng/ml,IL-10分别为(147.01±10.47)、(291.79±12.47)、(302.52±35.18)ng/ml.b、c组与a组比较,差异均有统计学意义(P＜0.01);b、c组IL-2、IL-12、IL-4比较,差异均有统计学意义(P＜0.05).d组IFN-γ、IL-2及IL-10分别为(497.42±29.03)、(739.77±18.58)及(120.33±13.21)ng/ml,与b组相比,差异均有统计学意义(P＜0.05).CsA、RPM及MPA对共刺激后Th1/Th2细胞因子的产生均有抑制作用,CsA对4种细胞因子产生的抑制作用强于RPM和MPA,其中对IL-2及IL-4的抑制作用更为明显.CsA与CTLA4 mAb有协同作用.共刺激后IL-12产生升高,MPA可抑制单刺激和共刺激后IL-12的产生,CsA和RPM对IL-12的产生无明显抑制作用.结论 CD28、CD40共刺激通路在淋巴细胞活化中起关键作用.CsA、RPM、MPA及CTLA4 mAb对共刺激后Th1/Th2细胞因子的产生均有抑制作用,CsA的抑制作用更为明显.CD40 L mAb使Th1细胞因子及IL-12水平下降,又促进Th2细胞因子(以IL-4为主)产生,该作用可能是抗CD40 L抗体诱导移植物存活期延长的机制之一.     

Contribution of CD4+ and CD8+ T cells and interferon-gamma to the progress of chronic rejection of kidney allografts: the Th1 response mediates both acute and chronic rejection

T cells mediating chronic rejection (CR) of human kidney allografts were characterized by comparing them with those mediating acute rejection (AR). Two lines of analysis were performed using biopsy specimens (23 CR and 8 AR). First, the extent of infiltration of CD4+ and CD8+ T cells into allografts was assessed from mRNA expression of CD4 and CD8. The group of CR specimens was not significantly different from the group of AR specimens in terms of the extent of CD4+ and CD8+ T cell infiltration, underlining the importance of the immunological contribution to the progress of CR. Second, Th1/Th2 polarization in infiltrating T cells was investigated by measuring mRNA expression of interferon gamma (IFN-gamma; a Th1 cytokine) and interleukin 4 (IL-4; a Th2 cytokine). IFN-gamma expression was detected in most CR specimens, and was not significantly different between the group of CR specimens and the group of AR specimens. On the other hand, IL-4 expression was detected in only two CR specimens and one AR specimen; from its pathological features, the AR in this last case was concomitant with CR. These results suggest that most cases of CR and of AR are mediated by Th1 mechanisms, although some cases of CR show features of both Th1 and Th2.     

Peritoneal T cell responses can be polarized toward Th1 or Th2 in children on chronic peritoneal dialysis

Peritoneal T cell responses can be polarized toward Th1 or Th2 in children on chronic peritoneal dialysis. Previous studies on the peritoneal immune system described the presence of activated T lymphocytes in peritoneal effluents from subjects on chronic peritoneal dialysis (CPD). Since Th1/Th2 polarized response can influence the outcome of specific infectious diseases, we investigated if activated Th1/Th2 cells can be detected in peritoneal effluents during peritoneal dialysis, in order to better understand the role of T cells in the mechanisms of peritoneal defense. We have studied 8 children (4 males, 4 females, mean age 5.8 +/- 5.7 years, range 0.3-13.4) on CPD. Peritoneal cells have been isolated from peritoneal effluents by centrifugation. Immunofluorescent staining of intracellular cytokines for flow cytometric analysis was used to detect the percentage of T cells producing either IFN-gamma (Th1) or IL-4 (Th2). In the initial study 3 months after CPD initiation, high percentages of IFN-gamma positive peritoneal T cells (38% and 63%) were detected in two subjects; this finding is consistent with a Th1 polarization of peritoneal T cells. In another subject, high percentages of IL-4 positive T cells (31%) were detected, suggesting a Th2 polarization of peritoneal T cell response. Small amounts of either Th1 or Th2 T cells (2-4%) were also detected in the other subjects. At the 1 year follow-up, Th1 polarization persisted in one subject (18% IFN-gamma positive peritoneal T cells), in another a shift from Th1 to Th2 was observed, and in the other subject a down regulation of both T cell subsets occurred. The finding that a predominance of T cells producing either IFN-gamma or IL-4 was found in 3 out of 8 children strongly suggests that peritoneal T cell responses can be polarized toward Th1 or Th2. The decrease of Th1 and/or Th2 polarized T cells in the peritoneum of 4 out of 6 subjects (after 1 year) suggests that CPD can play an immunosuppressive role on T cell peritoneal responses. Further studies are needed in order to define whether different T helper activation patterns are associated with a higher risk of peritoneal infection or of peritoneal damage.     

The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome

The aim of this study was to investigate the prevalence of interleukin (IL)-17-producing CD4+ T cells (Th17) and regulatory T (Treg) cells in children with primary nephrotic syndrome. The study cohort consisted of 62 children who were randomly divided into control, primary nephrotic syndrome, and isolated hematuria groups. Flow cytometric analysis revealed the presence of Th17 cells in the peripheral blood mononuclear cells (PBMCs) of 35 children and Tregs in the PBMCs of all children. In addition, mRNA expression of Th17-related factors [IL-17, -23p19 and retinoid orphan nuclear receptor (RORc)] and the concentration of plasma inflammatory mediators such as IL-6 and IL-1β were consistently detected in all children. Protein expression of IL-17 and transforming growth factor-β1 were also detected in renal biopsy tissue and compared between different groups. Patients with PNS were found to have an increased number of Th17 cells and decreased numbers of Tregs in their PBMCs, and there was significant difference in the prevalence of Th17 and Tregs between the patients with PNS and those with isolated hematuria. Our data show that among our study cohort, there was a dynamic equilibrium between Th17 and Treg cells in children with PNS following the development of PNS with apparent renal tubular epithelial cell and interstitium lesions. The dynamic interaction between Th17 and Treg cells may be important in the development of PNS.     

Characteristic cytokine products of Th1 and Th2 cells in hemodialysis patients.

Dysfunction of the host defense against infection in hemodialysis (HD) patients has major clinical and socioeconomic implications. T helper type 1 (Th1) and type 2 (Th2) cytokines are implicated in regulating the immune responses and, therefore, may be involved in impaired status. The present study was designed to examine Th1 and Th2 cytokine profiles in 22 stable HD patients (aged 63 +/- 11 years) and 22 healthy controls (aged 60 +/- 6 years). The T cell activity was significantly retarded in HD patients as compared with normal persons. The proportions of T cytotoxic/suppressor cells and natural killer cells were significantly higher in HD patients than in controls. In contrast, the proportions of T helper/inducer and B cells were significantly lower in HD patients than in controls. The production of interleukin (IL) 2, which is involved in cell-mediated immune responses, and the production of IL-4 and IL-10, which affect humoral immunity, were significantly lower in patients than in controls. The production of IL-12 by macrophages and of interferon gamma by Th1 cells was significantly higher in HD patients than in controls. The concentration of plasma sIL-2R was significantly higher in patients than in controls. These results suggest that both cellular immunity induced by Th1 and humoral immunity induced by Th2 decrease in HD patients, but that improved IL-12 secretion by macrophages activated natural killer cells to produce interferon gamma, which in turn induced macrophage activity.