Blood Th17 Research Articles

Effects of transcutaneous acupoint electrical stimulation on the imbalance of Th1, Th2, Th17 and Treg cells following thoracotomy of patients with lung cancer.

An imbalance in the various T lymphocytes, including T-helper (Th)1, Th2 and Th17 cells, and regulatory T (Treg) cells, has been associated with immune dysfunction, and may occur following thoracotomy of patients with lung cancer. The use of transcutaneous acupoint electrical stimulation (TAES) has previously been demonstrated to exert immunoregulatory effects; therefore, the present study aimed to evaluate whether TAES was able to attenuate postoperative immune suppression in patients with lung cancer. Thoracic surgical patients with lung cancer (n=27) underwent TAES (frequency, 2/100 Hz; intensity, 4-12 mA) at the bilateral large intestine 4, pericardium 6, small intestine 3 and San Jiao 6 acupuncture points for 30 min, prior to incision, and at 20, 44, 68, 92 and 116 h following thoracotomy. The number of Th1, Th2, Th17 and Treg cells, and the protein and mRNA expression levels of related cytokines were measured by flow cytometry, ELISA and polymerase chain reaction, respectively. The balance of Th1, Th2, Th17 and Treg cells in the peripheral blood of patients with lung cancer was disrupted following thoracotomy. TAES administration increased the percentage of Th1 and Th17 cells, the protein expression levels of interleukin (IL)-2 and interferon-γ, the mRNA expression levels of T-bet and RAR-related orphan receptor-γt, and decreased the percentage of Th2 cells, IL-10 protein expression levels, and GATA binding protein 3 mRNA expression levels. The results of the present study demonstrated that TAES was able to partially attenuate the postoperative immune depression of patients with lung cancer, by regulating the balance of Th1, Th2, Th17 and Treg cells, and the expression levels of related cytokines and transcription factors; therefore, TAES may be considered to be a promising strategy for treating postoperative immune dysfunction in patients with lung cancer.

Th17 cells reflect colon submucosal pathologic changes in active eosinophilic granulomatosis with polyangiitis.

BackgroundChronic eosinophilic pneumonia (CEP) or eosinophilic gastroenteritis (EG), or both, with asthma precede the onset of eosinophilic granulomatosis with polyangiitis (EGPA) in half of all EGPA patients. It is not known what determines whether patients with CEP or with EG following asthma will develop EGPA.MethodsWe studied 17 EGPA patients and 12 patients with CEP but without EGPA. We assayed serum ICAM-1, VCAM-1, and VEGF, and the percentage of peripheral blood CD4+ T cells producing IL-17 (Th17 cells), at both onset and remission. We also examined the numbers of submucosal eosinophils and the basement membrane-to-crypt and crypt-to-crypt distance to evaluate edema in the colon submucosa at onset and remission in EGPA and at onset in CEP.ResultsNine of 12 (75.0 %) CEP patients had symptoms or endoscopic findings. Colonic submucosal eosinophil counts and edema in EGPA at onset were greater than at remission or in CEP at onset. Th17 cells (%) and serum ICAM-1 levels at onset were greater in EGPA than in CEP. In EGPA, peripheral blood Th17 cells (%) were significantly correlated with serum ICAM-1 level, colonic submucosal eosinophil count, and degree of edematous change; inversely correlated with serum VEGF level; but not correlated with VCAM-1 level.ConclusionsEosinophilia and colonic submucosal edematous change were greater in EGPA than in CEP. The mechanism of vasculitis in EGPA appears related to increases in serum Th17 cell numbers and ICAM-1 levels and decreases in VEGF levels.

Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses.

BackgroundAntenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear.MethodTo assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo from 26 to 29 weeks of gestation to delivery. In a subset of participants (n = 80), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants, lymphocyte gene expression profiles were analyzed by PCR array.ResultIn supplemented group, increased concentrations of IL-10 (P < 0.000) and TNF-α (P = 0.05) with iCD3/iCD28 stimulation and IFN-γ (p = 0.05) with PHA stimulation were obtained compared to placebo group. No differences in the gene expression profile were noted between the two groups. However, PHA stimulation significantly induced the expression of genes encoding Th1 and Th2 cytokines and down-regulated a number of genes involved in T-cell development, proliferation and differentiation of B cells, signal transduction pathway, transcriptional regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD group).ConclusionThird-trimester high-dose vitD3 supplementation in healthy pregnant women had balanced effects on biomarkers of cord blood Th1 and Th2 responses.Trial registrationClinicalTrials.gov (NCT01126528).Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-016-0194-5) contains supplementary material, which is available to authorized users.

Correlation between Th17 and nTreg cell frequencies and the stages of progression in chronic hepatitis B.

Several studies have suggested that the balance of T helper 17 (Th17) and natural regulatory T (nTreg) cells in the Th17‑mediated immune response are critical in the pathogenesis of viral hepatitis. The aim of the present study was to examine the role of circulating Th17 and nTreg cells in the disease progression of hepatitis B virus (HBV) infection. A total of 40 patients with chronic HBV (CHB), 27 patients with HBV‑associated cirrhosis, 20 patients with HBV‑associated liver failure and 20 healthy controls were enrolled in the present study. The frequencies of Th17 and nTreg cells in the peripheral blood were examined using flow cytometry. Th17‑associated serum cytokine levels were measured using an enzyme‑linked immunosorbent assay. The results revealed a significantly higher frequency of circulating Th17 cells in the patients with CHB, cirrhosis and liver failure compared, with the normal controls, particularly in the patients with liver failure. The same trend was observed in the serum levels of interleukin (IL)‑17. The frequency of Th17 cells and the serum levels of IL‑17 were positively correlated with the levels of alanine aminotransferase and the prothrombin times. There was a significantly higher frequency of circulating nTreg cells in the patients with CHB, compared with the normal controls. The nTreg cell frequencies were significantly and positively correlated with plasma HBV DNA load, and were negatively correlated with Th17 frequencies in the cohort of patients with HBV. Taken together, the results suggested that Th17 cell‑mediated inflammation is associated with progression from CHB to cirrhosis, and to liver failure. Peripheral Th17 cell frequency and serum levels of IL‑17 may assisting in predicting the severity of liver damage and fibrosis.

Effects of Thalidomide on Peripheral Blood Th17 Cells of Patients with Multiple Myeloma

To explore the change of T help cell 17 (Th17) in the peripheral blood of patients with multiple myeloma (MM) before and after treatment with thalidomide. A total of 35 MM patients treated with thalidomide and 35 healthy controls were enrolled in this study. The percentage of Th17 cells were detected by flow cytometry. The mRNA levels of retinoid-related orphan receptor gamma-t (RORγt) were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and the plasm IL-17 levels were measured by enzyme linked immunosorbent assay (ELISA). The percentage of Th17 cells, the mRNA expression of RORγt and the plasm IL-17 levels in patients with MM were statistically higher than those in normal controls (P < 0.05). The percentage of Th17 cells was not correlate with the sex, age, disease type, globulin, immune globulin, light chain, M-protein and the proportion of plasmocytes (P > 0.05), but correlated with ISS stage, the level of β2-microglobulin and the plasm IL-17 levels (P < 0.05). The percentage of Th17 cells, the mRNA expression of RORγt and the plasm IL-17 levels in patients with response to thalidomide were statistically lower than those in patients before treatment (P < 0.05). The Th17 cells increase in the peripheral blood of patients with MM, the Th17 cells may participate in the occurrence of MM. Thalidomide may exert anti-MM through down-regulating Th17 cells.

Distribution of Th1, Th2 and Th17 in peripheral blood of patients with carotid atherosclerotic ischemic stroke

Objective To investigate the distribution of T helper cell 1 (Th1), Th2 and Th17 in peripheral blood of patients with carotid atherosclerotic ischemic stroke. Methods There were a total of 180 patients with carotid atherosclerotic ischemic stroke and 60 normal controls enrolled in this study. According to the degree of carotid artery stenosis, 180 patients were divided into 3 subgroups: mild stenosis group (N = 60), moderate stenosis group (N = 60) and severe stenosis group (N = 60). Flow cytometry (FCM) was used to test the proportion of Th1, Th2 and Th17 cells in peripheral blood. Results Compared with control group, the proportion of Th1 [(5.76 ± 1.81)% vs (3.54 ± 0.29)%, P = 0.000] and Th17 [(0.36 ± 0.13)% vs (0.18 ± 0.03)% , P = 0.000] cells in ischemic stroke group was significantly increased. There were statistical differences in the proportion of Th1 cells [(4.56 ± 0.55)%, (4.88 ± 0.42)% and (7.83 ± 1.69)%; P = 0.000] and Th17 cells [(0.23 ± 0.04)%, (0.34 ± 0.02)% and (0.50 ± 0.09)%; P = 0.000] in peripheral blood of patients with different degrees of carotid stenosis. The proportion of Th1 cells ( P = 0.001, 0.001) and Th17 cells ( P = 0.000, 0.001) in severe stenosis group were higher than those in mild and moderate stenosis groups, and the proportion of Th17 cells was higher in moderate stenosis group than that in mild stenosis group ( P = 0.000). Conclusions Th1 and Th17 cells participate in the pathological process of carotid atherosclerosis. As the degree of carotid atherosclerosis in patients with ischemic stroke is increased, the proportion of peripheral blood Th17 cells is increased, suggesting that cellular immune mechanism is involved in the occurrence and development of atherosclerosis and provide theoretical basis for the immune treatment of carotid atherosclerotic ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2016.09.008

Mutual Interaction of Basophils and T Cells in Chronic Inflammatory Diseases.

Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity receptor for IgE (FcεR1), release histamine, inflammatory mediators, and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid, and non-lymphoid tissues, and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2, and Th17 cells, as well as their potential role in IgE-independent non-allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases.

Research on the efficacy and mechanism of standardized house dust mite allergen vaccine to allergic rhinitis

The study was designed to analyze the efficacy of standardized house dust mite allergen vaccine to allergic rhinitis by subcutaneous injection and investigate the possible mechanism of specific immunotherapy (SIT). From January 2011 to December 2011 a prospective study was performed in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Nantong University, involving 90 patients with perennial AR, of whom 60 patients received Der p - SIT + pharmacotherapy after their approval and 30 received only pharmacotherapy. All patients were allergic to house dust mites. Symptom and medication scores were recorded three times: before the treatment, at the middle of treatment and at the end of treatment. Over a period of 1 yr. prior to and at the end of treatment, CD4⁺ CD25⁺ Foxp3⁺ Treg cells and Th17 cells were measured by flow cytometry. SPSS 21.0 software was used to analyze the data. The symptom scores using VAS and medication scores in AR patients treated with SIT and medication were reduced, the differences were significant (14.25 ± 6.40, 1.00 ± 0.84 vs. 32.18 ± 7.78, 3.12 ± 1.54, t value was 19.65, 10.71, both P < 0.05). The symptom of VAS score in medication group was reduced after treatment (30.30 ± 5.97 vs. 20.30 ± 5.79, t = 10.09, P < 0.05), but the medication score had not significant difference (P > 0.05). The frequency of Th17 cells in peripheral blood mononuclear cells were decreased in patients treated with SIT, whereas the frequency of Treg cells were increased (χ² value was 2.81, 2.80, both P < 0.05), but not in medication group. Both SIT and pharmacotherapy can improve symptoms of allergic rhinitis, but SIT can also reduce medication use. The effect of immunotherapy is better than drug treatment alone. The frequency of blood Th17 cells in peripheral blood mononuclear cells were decreased in patients treated with SIT, whereas the frequency of Treg cells were increased.

Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia

Introduction: Preeclampsia is one of the major causes of maternal and neonatal mortality. During pregnancy, the immune system must maintain the tolerance to the fetus, thus changes in the cytokine balance may result in a disturbed pregnancy. T helper cells play an important role in modulation of the immune system and are involved in this cytokine balance.Objective: Many studies have been performed to study the T cell composition in different compartments during pregnancy, although this is the first study in which T cells are evaluated in umbilical cord blood.Study design: Intracellular expression of INF-gamma, IL-17, IL-4 and forkhead foxP3 in CD4+ T cells was evaluated in umbilical blood from healthy pregnant and preeclamptic women using a flow cytometer.Results: Th2 and Treg cells levels were significantly diminished in preeclamptic compared to the healthy women, but no difference in Th1 and Th17 levels were found between both groups.Conclusions: Our data suggest that the cytokine balance is broken, encouraging the development of an exacerbated inflammatory response. Our results show that there is a shift, in the Th1/Th2, and the Th17/Treg balance, favoring skewness towards a proinflammatory status in the umbilical cord blood in preeclampsia.

Disturbed Th17/Treg Balance in Patients with Non-small Cell Lung Cancer.

The fine balance of T help-17 (Th17)/regulatory T(Treg) cells is crucial for maintenance of immune homeostasis. However, there is little information concerning the role played in non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC. Blood samples were collected from 19 patients with NSCLC and 19 healthy donors. Samples were processed to detect CD4(+)IL-17(+) Th17 cells and CD4(+)CD25(+)Foxp3(+) Treg cells by flow cytometry, and related gene expressions were assessed by real-time quantitative polymerase chain reaction. The concentrations of interleukin (IL)-1β, IL-6, IL-10, IL-17, IL-23, and transforming growth factor-beta (TGF-β1) were also measured by enzyme-linked immunosorbent assay analysis (ELISA). The frequency of circulating Th17 cells and Treg cells was increased in samples derived from patients with NSCLC, accompanied by the upregulation of Foxp3 and RORγt. However, a negative correlation between Treg cells and Th17 cells was found in patients with NSCLC. Additionally, the Th17/Treg ratio and the related cytokines were also significantly higher in patients with NSCLC than in healthy controls. Furthermore, the frequency of Th17 cells was positively correlated with IL-1β, IL-6, and IL-23 in patients with NSCLC, and the frequency of Treg cells was positively correlated with TGF-β1 and IL-10. More importantly, the Th17/Treg ratio was positively correlated with the CEA concentrations in patients with NSCLC. Our data indicated that Th17 and Treg subset are involved in the immunopathology of NSCLC. Distinct cytokine environment might play a key role in the differentiation of the Th17 and Treg cells in NSCLC. Reconstituting an adequate balance between Th17 and Treg may be beneficial in the treatment of NSCLC.

Therapeutic effect of narrow band - utraviolet B combined with interferon - alpha - 2b for the treatment of mycosis fungoides and its correlation with Treg/Th17 cells

Objective To evaluate the therapeutic effect of narrow band-ultraviolet B (NB-UVB) alone or in combination with interferon-alpha-2b (INF - alpha-2b) for mycosis fungoides (MF), and to assess the correlation between the therapeutic effect and peripheral blood regulatory T (Treg)/T helper type 17 (Th17) cells. Methods Thirty-three patients with stage IA to IIA MF were randomly divided into two groups: NB-UVB group (n = 15) receiving NB-UVB radiation alone, combined group (n = 18) treated with NB-UVB radiation and intramuscular injection of INF-alpha-2b. Ten healthy volunteers were selected as the control group. Peripheral blood samples were collected before and 9 months after the start of treatment. Flow cytometry was performed to determine the percentages of Treg cells and Th17 cells. Statistical analysis was carried out by using t test, one-way analysis of variance, and Fisher's exact test. Results The average treatment duration was 9 months among these patients. Therapeutic outcomes were significantly better in the combined group than in the NB-UVB group (P= 0.023). Among the 15 patients in the NB-UVB group, 6 achieved complete remission, 3 partial remission, 6 showed no response; of the 18 patients in the combined group, 12 experienced complete remission, 5 partial remission, and 1 showed no response. Before the treatment, the percentages of both Treg and Th17 cells in peripheral blood were significantly higher in the NB-UVB group and combined group than in the control group (both P 0.05). After the treatment, the percentages of both Treg and Th17 cells in the NB - UVB group and combined group significantly decreased compared with those before the treatment, but were still higher than those in the control group (both P 0.05) after the treatment. Conclusions The therapeutic effect of NB-UVB radiation combined with intramuscular INF-alpha-2b is superior to that of NB - UVB radiation alone for MF, which may be associated with the degree of decrease in peripheral blood Treg and Th17 cells. Key words: Ultraviolet therapy; Interferon-alpha; Treatment outcomes; T-lymphocytes, regulatory; Th17 cells; Mycosis fungoides

Docosahexaenoic Acid Alleviates Atopic Dermatitis in Mice by Generating T Regulatory Cells and M2 Macrophages

Han et al. (this issue) describe a novel mechanism by which docosahexaenoic acid (DHA) may suppress atopic dermatitis symptoms in mice. They find that DHA induces FoxP3 T regulatory cells in vivo, M2 macrophages drive transforming growth factor-β and IL-10 conversion of CD4 T cells to CD4 FoxP3 T regulatory cells in vitro, and DHA-treated M2 macrophages suppress atopic dermatitis in mice.

Relationship Between Serum Interleukin-17F Level and Severity of Atopic Dermatitis in Children

Background: Recent discovery of the Th17 pathway is providing new opportunities for understanding chronic immune-mediated diseases. The Th17 pathway has been historically associated with chronic inflammatory diseases such as psoriasis, multiple sclerosis, and rheumatoid arthritis. Among Th17 cytokines, pathogenic roles of IL-17A and IL-17F in asthma have been well described. Recently, the number of peripheral blood Th17 cells was found to correlate with disease severity in patients with atopic dermatitis (AD). This study aimed to investigate serum IL-17F levels in children with AD and to correlate this with severity of the disease. Methods: Enzyme-linked immunosorbent assay was used to measure IL-17F levels in the sera of 228 patients with AD and 62 control children. The SCORing Atopic Dermatitis (SCORAD) tool was used to determine the severity of disease. Results: The mean serum level of IL-17F in children with AD was significantly higher than that in the control group (p<0.05) Serum IL-17F levels were also higher in patients with severe AD than in those with mild AD (p<0.001), and IL-17F levels and SCORAD scores were positively correlated (p<0.05). Conclusions: Serum IL-17F level might be a useful marker in children with AD.

Th1, Th2, Th17 and Treg levels in umbilical cord blood of preeclamptic women. (HUM1P.300)

Abstract Preeclampsia is one of the major causes of maternal and neonatal mortality. The immune system during pregnancy has to maintain the tolerance to the fetus, thus changes in the cytokine balance may result in a disturbed pregnancy. T helper cells play an important role in the modulation of the immune system. Many studies have been performed to study the T cell composition in different compartments during pregnancy, although this is the first study in which the levels of Th1, Th2, Th17 and Treg cells are evaluated in umbilical cord blood from normal and preeclamptic women. We did not find any difference in Th1 and Th17 levels between groups, but Th2 and Treg levels were significantly diminished in preeclamptic women. Even if we found no differences between pro-inflammatory profiles, their counterparts Th2 and Treg are diminished, suggesting that the balance is broken encouraging the development of an exacerbated inflammatory response. Our results show that there is a shift, not only in the Th1/Th2, but also in the Th17/Treg balance, favoring skewness towards a proinflammatory status in preeclampsia, so the innate and adaptative immune system are involved in the development of an exaggerated maternal systemic inflammation.

High peripheral blood th17 percent associated with poor lung function in cystic fibrosis.

People with cystic fibrosis (CF) have been reported to make lung T cell responses that are biased towards T helper (Th) 2 or Th17. We hypothesized that CF-related T cell regulatory defects could be detected by analyzing CD4+ lymphocyte subsets in peripheral blood. Peripheral blood mononuclear cells from 42 CF patients (6 months–53 years old) and 78 healthy controls (2–61 years old) were analyzed for Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17+), Treg (FOXP3+), IL-10+ and TGF-β+ CD4+ cells. We observed higher proportions of Treg, IL-10+ and TGF-β+ CD4+ cells in CF adults (≥ 18 years old), but not children/adolescents, compared with controls. Within the CF group, high TGF-β+% was associated with chronic Pseudomonas aeruginosa lung infection (p < 0.006). We observed no significant differences between control and CF groups in the proportions of Th1, Th2 or Th17 cells, and no association within the CF group of any subset with sex, CFTR genotype, or clinical exacerbation. However, high Th17% was strongly associated with poor lung function (FEV1 % predicted) (p = 0.0008), and this association was strongest when both lung function testing and blood sampling were performed within one week. Our results are consistent with reports of CF as a Th17 disease and suggest that peripheral blood Th17 levels may be a surrogate marker of lung function in CF.

Increased circulating Th17 cells and elevated serum levels of TGF‐beta and IL‐21 are correlated with human non‐segmental vitiligo development

Although non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, the detailed immune mechanisms have not yet been fully elucidated. Th17 cells have been identified to be implicated in human autoimmune diseases. In this study, the frequencies of peripheral blood Th17 cells and serum levels of IL-17A and Th17 cell-related cytokines were examined in 45 patients with active NSV compared to 45 race-, gender-, and age-matched healthy controls. Our results showed increased circulating Th17 cell frequencies and elevated serum IL-17A, TGF-β1, and IL-21 levels in patients with NSV. Meanwhile, the increased Th17 cell frequencies are positively correlated with serum TGF-β1 level, and the body surface area of lesions is positively correlated with elevated TGF-β1 and IL-21 levels and Th17 cell frequencies. Furthermore, positive correlation was identified between Th17 and Th1 cell frequencies in patients with NSV. These results further indicate the potential involvement of Th17 cells and the collaborative contribution of Th17 and Th1 in NSV development, and suggest that the elevated serum TGF-β1 and IL-21 levels could contribute to enhanced Th17 cell differentiation in NSV.

INFLUENCE OF CpG ODN 2006 OLIGODEOXYNUCLEOTIDE ON CYTOKINE PRODUCTION BY BLOOD CELLS OF HUMANS VACCINATED AGAINST PLAGUE

This study presents data upon the effects of CpG oligonucleotide substance (CpG ODN 2006). The commercial preparation was applied in vitro as a single agent, or in combination with various cytokine production inducers. Spontaneous and induced cytokine levels were tested in cultures of human blood cells taken from the persons before and after anti-plague vaccination. It has been shown that the vaccination had no effect upon spontaneous production of cytokines participating in innate (IL-8, TNFα) and adaptive (IFNγ, IL-4) immunity. CpG ODN 2006 proved to exert effects upon functional activity of human blood Th1 and Th2 pro-inflammatory cytokines after the first vaccination with live anti-plague vaccine, being reflected as higher Th1/ proinflammatory (IL-17 and IFNг) and Th2/ antiinflammatory (IL-4) cytokine production. Postvaccination changes of IgM, IgG, IgA, and IgE contents were non-significant. Following repeated vaccination, the CpG ODN 2006 induced an increase of IL-4 and IL-17 production in blood cells, as well as decrease in IFNг levels. Thus, the ability of CpG ODN 2006 to activate the cells participating in innate and adaptive immunity opens some prospects for usage of this oligodeoxynucleotide in the development of more efficient anti-plague vaccines.

The TH17/Treg Imbalance in Rheumatoid Arthritis and Relation to Disease Activity

Objectives: T regulatory cells (Treg) and proinflammatory TH17 cells are newly identified T lymphocyte subsets, which have significant effects on autoimmunity and inflammation. Tregs play key role in the maintenance of self-tolerance. TH17/Treg disturbed balance has been reported to contribute to several autoimmune diseases.Our aim was to assess the Treg/TH17 pattern and TH17 related cytokines, in peripheral blood of Egyptian rheumatoid arthritis patients, and their relation to disease activity score (DAS). Analyzing IL17A and IL23 as indicators of TH17 function, was to study the effect of TH17 in RA.Methods: 100 Egyptian rheumatoid arthritis patients, divided into Group I (14), Group II (48), Group III (38), with low 5.1, activity DAS score respectively; and 50 healthy age and sex matched controls were enrolled. Peripheral blood TH17 and Treg (CD4+CD25+Foxp3+) frequencies were analyzed by flowcytometry, and the serum levels of interleukins (IL17A), (IL23) were determined by ELISA.Results: Active RA patients (groups II and III) revealed an obvious increase in peripheral TH17 frequencies, and levels of TH17-related cytokines, and a significant decrease in Treg (CD4+CD25+Foxp3+) frequencies in group III, when compared to healthy controls. TH17/Treg ratios were positively correlated with serum concentrations of IL17A and IL23 cytokines. Frequencies and levels showed statistical significant correlation with DAS scoring.Conclusions: Our study indicated that TH17/Treg balance was disturbed in peripheral blood of RA patients, leading to an increase of proinflammatory cytokines, correlating with DAS, and suggesting an important role in the development of RA.

Change of Th1, Th17 and Th22 cells in peripheral blood of patients with lupus nephritis and its clinical implication

Objective To investigate the expression of T-helper (Th)1,Th17 and Th22 cells in peripheral blood and cytokines in serum of patients with lupus nephritis (LN) and its clinical significance.Methods The proportion of Th1,Th17 and Th22 cells in peripheral blood of 20 LN patients and 20 healthy controls were evaluated by flow cytometry; the concentration of cytokines including interferon (IFN)-γ,interleukin (IL)-17 and IL-22 were measured by ELISA.The correlation between proportion of Th 17 and Th22 cells and IL-17,IL-22,systemic lupus erythematosus disease activity index (SLEDAI) were analyzed.Results The proportion of Th17 cells increased (P ＜ 0.05),the proportion of Th22 cells decreased (P ＜ 0.05),the proportion of Th 1 cells did not change too much (P ＞ 0.05) in LN patients compared with healthy controls; the concentration of serum IL-17 increased (P ＜ 0.05),the concentration of serum IL-22 decreased (P ＜ 0.05),the concentration of serum IFN-γ did not change too much (P ＞ 0.05) in LN patients compared with healthy controls.The proportion of Thl7 cells correlated positively with concentration of serum IL-17 and SLEDAI in LN patients (r =0.721,P ＜ 0.05; r =0.225,P ＜ 0.05).There was a positive correlation between the proportion of Th22 cells and concentration of serum IL-22 (r =0.489,P ＜ 0.05),no statistical correlation between the proportion of Th22 cells and SLEDAI (r =0.241,P ＞ 0.05).Conclusion The abnormal expression of Th 17 and Th22 may play an important role in LN disease pathogenicity. Key words: Lupus nephritis; T-helper 1; T-helper 17; T-helper 22

Immunosuppression with tacrolimus improved reproductive outcome of women with repeated implantation failure and elevated peripheral blood TH1/TH2 cell ratios.

We evaluated the clinical efficacy of immunosuppressive treatment with tacrolimus for repeated implantation failure (RIF) patients who have elevated in T helper (Th1)/Th2 cytokine producing cell ratios. This was a prospective cohort study of treatment for RIF patients (n=42) with elevated peripheral blood Th1 (CD4(+) /IFN-γ(+) )/Th2 (CD4(+) /IL-4(+) ) cell ratios at the Sugiyama clinic between November 2011 and October 2013. Twenty-five patients were treated with tacrolimus (treatment group) and 17 received no treatment (control group). Treatment group received tacrolimus 2days before embryo transfer and continued until the day of the pregnancy test, for a total of 16days. The daily dose of tacrolimus (1-3mg) was determined based on the degree of the Th1/Th2 cell ratio. The clinical pregnancy rate of the treatment group was 64.0%, which was significantly higher than that of the control group (0%) (P<0.0001). In the treatment group, the miscarriage rate was 6.3%, the live birthrate was 60.0% (P<0.0001). There was no significant side-effect from tacrolimus in treatment group. No one developed obstetrical complications during pregnancy. An immunosuppressive treatment using tacrolimus improved pregnancy outcome of repeated implantation failure patients with elevated Th1/Th2 ratios.