OBJECTIVETo compare the differences of the T helper cell reconstitution kinetics between HLA matched or HLA mismatched allo-HSCT through exploring the reconstitution kinetics of CD4+ CD25+Foxp3+ cells (CD4+ Treg), CD8+CD25+Foxp3+ cells (CD8+Treg), CD4+CD25-CD127+ conventional T cells (Tcon) and the secretion of IL-17a and IFN-γ in CD4+ T cells (Th17 and Th1 cells) or CD8+ T cells (Tc17 and Tc17 cells) post allogeneic hematopoietic stem cells transplantation (allo-HSCT).

METHODSFrom December 2011 to October 2012, the peripheral blood (PB) of 20 patients undergoing HLA matched (10 patients) or mismatched (10 patients) allo- HSCT without acute graft-versus-host disease (aGVHD) and of 10 related healthy donors were collected to analyze the expression of CD25+Foxp3+, IL-17a, IFN-γ and CD127 expression through 8-colour Flow cytometer.

RESULTS(1) The reconstitution kinetics of CD3+ T cells, CD4+ T cells, CD8+ T cells absolute numbers were comparable within 2 month post HLA matched and mismatched transplantation. (2)The absolute numbers of CD4+ Treg cells[+30 d, 8.46 (0.36-27.41) cells/μl 1.10 (0.04-8.03) cells/μl, P<0.05; +60 d, 8.50 (1.16-36.20) cells/μl vs 2.73 (0.34-6.84) cells/μl, P<0.05], Tcon cells[+30 d, 72.69 (3.85-211.73) cells/μl vs 13.41 (0.48-96.17) cells/μl, P<0.05; +60 d, 100.85 (16.28-267.20) cells/μl vs 47.75 (6.34-143.04) cells/μl, P<0.05], as well as Th17 cells[+30 d, 2.34 (0.02-6.87) cells/μl vs 0.20 (0.02-1.34) cells/μl, P<0.05; + 60 d, 1.90 (0.36- 7.82) cells/μl vs 0.46 (0.03-1.39) cells/μl, P<0.05]and Tc17 cells[+ 30 d, 1.08 (0.07-15.03) cells/μl vs 0.25 (0.01- 0.81) cells/μl, P<0.05;+60 d, 1.85 (0.63-26.57) cells/μl vs 0.46 (0.01-3.66) cells/μl, P<0.05]within 2 month post HLA matched HSCT were significantly higher than those post HLA- mismatched HSCT. However, the absolute numbers of Th1 cells or Tc1 cells within 2 month post HLA-matched or HLA-mismatched HSCT were comparable. (3) The ratio of Th1 and Th17 cells, or the ratio of Tc1 and Tc17 cells were significantly higher within 2 month post HLA-mismatched allo-HSCT compared to those post HLA-matched HSCT.

CONCLUSIONThe reconstitution kinetics of T helper cells subset were different at early stage post HLA-matched or HLA-mismatched allo-HSCT, which might be help to explain the different rate or the different involved organ of the acute graft-versus-host diseases (aGVHD) post HLA-matched or -mismatched allo-HSCT.

Adult ; Female ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th1 Cells ; Th17 Cells ; Transplantation, Homologous ; Young Adult

Animals ; CD4-Positive T-Lymphocytes ; immunology ; Humans ; Periodontal Diseases ; immunology ; pathology ; T-Lymphocytes, Regulatory ; immunology ; Th1 Cells ; immunology ; Th17 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVETo study the effects of huai qi huang, a traditional Chinese medicine, on cytokines Th1, Th2 and Th17 levels and alveolar macrophage phagocytosis in asthmatic rats sensitized by ovalbumin (OVA).

METHODSForty male Sprague-Dawley rats were randomly divided into five groups: normal control, untreated asthma, budesonide-treated, huai qi huang-treated and budesonide+huai qi huang-treated asthma (n=8 each). Asthma was induced by OVA sensitization and challenge. The levels of IL-4, IFN-γ and IL-17 in plasma and bronchoalveolar lavage fluid (BALF) were measured using ELISA. The phagocytosis of alveolar macrophages which were isolated and purified from BALF was evaluated by the colorimetric assay.

RESULTSThe levels of IL-4 and IL-17 increased, in contrast, the IFN-γ level decreased in plasma and BALF in the untreated asthma group compared with those in the normal control group. The IFN-γ level in the huai qi huang-treated asthma group was higher than that in the untreated asthma group. The IFN-γ level increased and the IL-17 level decreased more significantly in the budesonide+huai qi huang-treated asthma group when compared with the budesonide and huai qi huang alone treatment groups. The phagocytosis of alveolar macrophages in the untreated asthma group was lower than that in the normal control group. Huai qi huang alone or combined with budesonide increased the phagocytosis of alveolar macrophages compared with the normal control, untreated asthma and budesonid-treated asthma groups. The levels of IFN-γ in plasma and BALF were positively correlated with the phagocytosis of alveolar macrophages.

CONCLUSIONSThe levels of IL-4 and IL-17 increase and the IFN-γ level decreases in plasma and BALF, and the phagocytosis of alveolar macrophages decreases in asthmatic rats. Huai qi huang treatment may increase the IFN-γ expression in plasma and BALF and the phagocytosis of alveolar macrophages in asthmatic rats. There is a synergistic effect between huai qi huang and glucocorticoids.

Animals ; Asthma ; drug therapy ; immunology ; Cytokines ; biosynthesis ; Macrophages, Alveolar ; drug effects ; immunology ; Male ; Medicine, Chinese Traditional ; Phagocytosis ; drug effects ; Rats ; Rats, Sprague-Dawley ; T-Lymphocytes, Helper-Inducer ; immunology ; Th1 Cells ; immunology ; Th17 Cells ; immunology ; Th2 Cells ; immunology

Th2 cell immunity is required for host defense against helminths, but it is detrimental in allergic diseases in humans. Unlike Th1 cell and Th17 cell subsets, the mechanism by which dendritic cells modulate Th2 cell responses has been obscure, in part because of the inability of dendritic cells to provide IL-4, which is indispensable for Th2 cell lineage commitment. In this regard, immune cells other than dendritic cells, such as basophils and innate lymphoid cells, have been suggested as Th2 cell inducers. More recently, multiple independent researchers have shown that specialized subsets of dendritic cells mediate Th2 cell responses. This review will discuss the current understanding related to the regulation of Th2 cell responses by dendritic cells and other immune cells.
Basophils ; Dendritic Cells* ; Helminths ; Humans ; Interleukin-4 ; Lymphocytes ; Th1 Cells ; Th17 Cells ; Th2 Cells*

Asthma is a chronic obstructive airway disease that involves inflammation of the respiratory tract. Biological contaminants in indoor air can induce innate and adaptive immune responses and inflammation, resulting in asthma pathology. Epidemiologic surveys indicate that the prevalence of asthma is higher in developed countries than in developing countries. The prevalence of asthma in Korea has increased during the last several decades. This increase may be related to changes in housing styles, which result in increased levels of indoor biological contaminants, such as house dust mite-derived allergens and bacterial products such as endotoxin. Different types of inflammation are observed in those suffering from mild-to-moderate asthma compared to those experiencing severe asthma, involving markedly different patterns of inflammatory cells and mediators. As described in this review, these inflammatory profiles are largely determined by the involvement of different T helper cell subsets, which orchestrate the recruitment and activation of inflammatory cells. It is becoming clear that T helper cells other than Th2 cells are involved in the pathogenesis of asthma; specifically, both Th1 and Th17 cells are crucial for the development of neutrophilic inflammation in the airways, which is related to corticosteroid resistance. Development of therapeutics that suppress these immune and inflammatory cells may provide useful asthma treatments in the future.
Allergens ; Asthma ; Developed Countries ; Developing Countries ; Dust ; Housing ; Inflammation ; Korea ; Neutrophils ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; Respiratory System ; Stress, Psychological ; T-Lymphocytes, Helper-Inducer ; Th17 Cells ; Th2 Cells

CD4+ T lymphocytes play a major role in regulation of adaptive immunity. Upon activation, naive T cells differentiate into different functional subsets. In addition to the classical Th1 and Th2 cells, several novel effector T cell subsets have been recently identified, including Th17 cells. There has been rapid progress in characterizing the development and function of Th17 cells. Here I summarize and discuss on the genetic controls of their differentiation and emerging evidence on their plasticity. This information may benefit understanding and treating immune diseases.
Animals ; CD4-Positive T-Lymphocytes/cytology/*immunology ; Cell Differentiation ; Cell Lineage ; Cytokines/*genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Humans ; Interleukin-17/immunology/metabolism ; T-Lymphocytes, Regulatory ; Th1 Cells/immunology ; Th17 Cells/*immunology ; Th2 Cells/immunology ; Transcription Factors/*genetics ; Transcription, Genetic

Background: Immune disorder is an important feature of patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC). We investigated the expression of circulatory T helper type (Th) 1, Th2, and Th17 cells to explore the early immune alteration in OHCA patients after ROSC. Methods: During July-September 2016 and March-September 2017, 65 consecutive OHCA patients with ROSC >12 h and 30 healthy individuals were enrolled in this study. Clinical and 28-day survival data were collected. Peripheral blood samples were analyzed to evaluate the expression of Th1/Th2/Th17 cells by flow cytometry from OHCA patients after ROSC on days 1 and 3 and from healthy individuals. Results: Compared with healthy individuals, T lymphocyte counts and Th1 cell counts decreased on days 1 and 3 after ROSC (1464 [1198, 2152] vs. 779 [481, 1140] vs. 581 [324, 1118]/μl, χ = 30.342, P < 0.001; 154 [90, 246] vs. 39 [19, 78] vs. 24 [12, 53]/μl, χ = 42.880, P < 0.001), and Th2 and Th17 cell counts decreased on day 3 (17.0 [10.8, 24.0] vs. 9.0 [3.0, 15.5]/μl, Z = -3.228, P = 0.001; 4.7 [2.7, 9.1] vs. 2.7 [1.0, 6.5]/μl, Z = -2.294, P = 0.022). No change in CD4+/CD3+ lymphocyte ratio was seen on day 1 or day 3 (57.9 [49.4, 63.0] vs. 55.4 [46.5, 66.5] vs. 55.4 [50.2, 67.0]%, χ = 0.171, P = 0.918). Th1/CD4+ lymphocyte ratio decreased on days 1 and 3 (19.0 [14.0, 24.9] vs. 9.3 [4.6, 13.9] vs. 9.5 [4.9, 13.6]%, χ = 25.754, P < 0.001), and Th2/CD4+ lymphocyte ratio increased on day 1 and decreased on day 3 (1.9 [1.2, 2.5] vs. 2.5 [1.6, 4.0] vs. 1.9 [1.6, 3.8]%, χ = 6.913, P = 0.032). Th1/Th2 cell ratio also decreased on both days (9.4 [7.3, 13.5] vs. 3.1 [1.9, 5.6] vs. 4.2 [2.8, 5.9], χ = 44.262, P < 0.001). Despite an upward trend in the median of Th17/CD4+ lymphocyte ratio in OHCA patients, there was no significant difference compared with healthy individuals (0.9 [0.4, 1.2] vs. 0.7 [0.4, 1.2] vs. 0.6 [0.3, 1.0]%, χ = 2.620, P = 0.270). The dynamic expression of Th1/Th2/Th17 cells on days 1 and 3 were simultaneously analyzed in 28/53 OHCA patients who survived >3 days; patients were divided into survivors (n = 10) and nonsurvivors (n = 18) based on 28-day survival. No significant differences in Th1/Th2/Th17 cell counts, ratios in CD4+ lymphocytes, and Th1/Th2 cell ratio were seen between survivors and nonsurvivors on both days (all P > 0.05). There was no difference over time in both survivors and nonsurvivors (all P > 0.05). Conclusion Downregulated T lymphocyte counts, including Th1/Th2/Th17 subsets and Th1/Th2 cell ratio imbalance, occur in the early period after ROSC, that may be involved in immune dysfunction in OHCA patients.
Aged ; Cardiopulmonary Resuscitation ; Female ; Humans ; Male ; Middle Aged ; Out-of-Hospital Cardiac Arrest ; immunology ; therapy ; Th1 Cells ; Th17 Cells ; Th2 Cells

OBJECTIVETo observe the effect of Modified Zuoguiwan (MZ) on the balance between helper T cell subsets 17 (Th17) and regulatory T cell subsets (Treg) in estrogen deficiency induced bone loss mice and to explore its mechanism.

METHODSTotally 50 BALB/c mice were divided into the sham-operation group, the ovariectomy model group, the low dose MZ group, the middle dose MZ group, and the high dose MZ group by random digit table, 10 in each group. Mice in the low, middle, and high dose MZ groups were respectively administered with MZ at the daily dose of 7.25, 14.50, and 29.00 g/kg by gastrogavage, 0.5 mL each time for 12 successive weeks. Meanwhile, mice in the sham-operation group and the ovariectomy model group were administered with equal volume by gastrogavage, 0.50 mL each time. The serum estradiol (E2) level was assessed by enzyme linked immunosorbent assay (ELISA). Bone mineral density (BMD) of thigh bone was measured with dual energy X ray absorptiometry. In addition, the population of Th17/Treg subsets in spleen mononuclear cells was analyzed by extracellular and intracellular staining method using flow cytometry. Moreover, the mRNA expression of IL-17A and TGF-β in the spleen mononuclear cells was detected by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCompared with the sham-operation group, both E2 and BMD significantly decreased, the percentage of Th17 subset and Th17/Treg ratio both increased, the percentage of Treg subset obviously decreased, the expression of IL-17A mRNA significantly increased, and the expression of TGF-β mRNA significantly decreased in the ovariectomy model group (all P < 0.05). Compared with the model group, BMD obviously increased, the percentage of Th17 subset and Th17/Treg ratio both decreased, the percentage of Treg subset obviously increased, the expression of IL-17A mRNA significantly decreased, and the expression of TGF-β mRNA significantly increased in the middle dose MZ group and the high dose MZ group (all P < 0. 05). Correlation analyses showed that BMD was positively related to both the serum E2 level and the percentage of Treg subset (P < 0.05), but negatively related to the percentage of Th17 subset (P < 0.05). In addition, the serum E2 level was positively related to the percentage of Treg subset, but obviously negatively related to that of Th17 subset (P < 0.05).

CONCLUSIONSThere was correlation between Th17/Treg imbalance and E2 deficient bone loss. MZ could decrease the proportion of Th17 subset, but elevate the proportion of Treg subset in E2 deficient bone loss mice. It could achieve therapeutic effect through adjusting the balance of Th17/Treg in E2 deficient bone loss mice.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Estrogens ; deficiency ; metabolism ; Female ; Flow Cytometry ; Humans ; Interleukin-17 ; Mice ; Mice, Inbred BALB C ; Osteoporosis, Postmenopausal ; drug therapy ; RNA, Messenger ; Spleen ; T-Lymphocyte Subsets ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th17 Cells ; Transforming Growth Factor beta ; metabolism

OBJECTIVE: To explore the effects and mechanisms of the long-snake moxibustion on ankylosing spondylitis (AS) based on Th17/Treg/Th1 immune imbalance. METHODS: A total of 60 AS patients were randomized into an observation group and a control group, 30 cases in each one. In the observation group, the long-snake moxibustion therapy was used on the acupoints of the governor vessel from Dazhui (GV 14) to Yaoshu (GV 2) as well as the bilateral Jiaji (EX-B 2) alternatively. The moxibustion was given once a day, for 7 days continuously as one course. There were 3 days at the interval between the courses and 4 courses were required. In the control group, the routine western medication was provided, the salazosulfapyridine combined with non-steroidal anti-inflammatory drugs were used, for 7 days continuous as one course. A total of 4 courses of medication were required. The enzyme linked immunosorbent assay (ELISA) was adopted to determine the levels of interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α). The real-time quantification polymerase chain reaction (RT-PCR) was used to determine the mRNA expressions of the specific transcription factors, FoxP3 and T-bet of the helper 17 cells (Th17), regulatory T cells (Treg) and T helper 1 cells (Th1). The flow cytometry was applied to determine the rates of Treg, Th1 and Th17, as well as the changes of the inflammatory reaction index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The therapeutic effects were compared between the two groups. RESULTS: After treatment, the total effective rate was 93.3% (28/30) in the observation group, which was better than 86.7% (26/30) in the control group (<0.05). After treatment, the levels of CRP, ESR, IL-6, IL-17, IL-23 and TNF-α, as well as the rate of Th17 were reduced significantly as compared with those before treatment in the observation group (all <0.05). The mRNA expressions of FoxP3 and T-bet and the rates of Treg and Th1 were increased as compared with those before treatment (all <0.05). The change degree in the observation group was significant as compared with the control group (all <0.05). In the control group, the levels of CRP, ESR, IL-6, IL-17, IL-23 and TNF-α, as well as the rate of Th17 were reduced, and the mRNA expressions of FoxP3 and T-bet and the rates of Treg and Th1 were increased after treatment. But the changes were not significant as compared with those before treatment (all >0.05). CONCLUSION The long-snake moxibustion effectively relieves the clinical symptoms in AS patients and regulates the Th17/Treg/Th1 immune imbalance. Its effect target is probably related to the modulation of the AS immune derangement and the inflammatory responses induced by immune derangement so as to achieve the dual-positive regulatory effect.
Animals ; Humans ; Lymphocyte Count ; Moxibustion ; Snakes ; Spondylitis, Ankylosing ; therapy ; T-Lymphocytes, Regulatory ; Th1 Cells ; Th17 Cells

BACKGROUND: CD4+Fop3+ regulatory T cells (Tregs) are needed to maintain peripheral tolerance, but their role in the development of autoimmune arthritis is still debated. The present study was undertaken to investigate the mechanism by which Tregs influence autoimmune arthritis, using a mouse model entitled K/BxN. METHODS: We generated Treg-deficient K/BxNsf mice by congenically crossing K/BxN mice with Foxp3 mutant scurfy mice. The arthritic symptoms of the mice were clinically and histopathologically examined. The proportions and activation of CD4+ T cells and/or dendritic cells were assessed in the spleens, draining lymph nodes and synovial tissue of these mice. RESULTS: K/BxNsf mice exhibited earlier onset and more aggressive progression of arthritis than their K/BxN littermates. In particular, bone destruction associated with the influx of numerous RANKL+ cells into synovia was very prominent. They also contained more memory phenotype CD4+ T cells, more Th1 and Th2 cells, and fewer Th17 cells than their control counterparts. Plasmacytoid dendritic cells expressing high levels of CD86 and CD40 were elevated in the K/BxNsf synovia. CONCLUSION: We conclude that Tregs oppose the progression of arthritis by inhibiting the development of RANKL+ cells, homeostatically proliferating CD4+ T cells, Th1, Th2 and mature plasmacytoid dendritic cells, and by inhibiting their influx into joints.
Animals ; Arthritis ; Dendritic Cells ; Joints ; Lymph Nodes ; Memory ; Mice ; Peripheral Tolerance ; Phenotype ; Spleen ; Synovial Fluid ; Synovial Membrane ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Th17 Cells ; Th2 Cells