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This study aimed to investigate the anti-asthma effects of Ephedrae Herba polysaccharides (PE) and possible mechanisms related to immune inflammatory response. An asthma model was established in rats using ovalbumin (OVA). Seventy rats were randomly assigned to five groups: control, model, dexamethasone (DEX, 0.075 mg/kg), low dose polysaccharides (LPE, 137.71 mg/kg) and high dose polysaccharides (HPE, 275.42 mg/kg). The cough and asthma were used to evaluate the basic state of asthmatic rats. Histological studies were evaluated by hematoxylin and eosin (H&E), Masson, and periodic acid-schiff (PAS) staining. The levels of interferon-γ (IFN-γ), interleukin (IL)-4, immunoglobulin E (IgE), tumor necrosis factor α (TNF-α), and IL-17A in bronchoalveolar lavage fluid (BALF), and the levels of transforming growth factor β1 (TGF-β1), IL-6, and IL-10 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of Ifn-γ , Il-4 , Tgf-β1 , Il-6 , Il-10 , Tnf-α , Il-13 , and Il-17a were evaluated by quantitative real-time reverse transcription (qRT)-PCR. The dendritic cell (DCs), T helper cell (Th), natural killer cell (NK), regulatory T cell (Treg), and Th17 cells in blood, the lymphocytes, macrophages and neutrophils in spleen, and cell apoptosis and reactive oxygen species (ROS) in lung were analysed by flow cytometry (FCM). Immunohistochemistry (IHC) was used to stain DCs (CD11c+, CD86+, and CD80+), macrophages (CD68+), and neutrophils (MPO+) in the spleen and lung. The protein levels of IL-17A, CD11c, CD86, and CD80 in lung were measured by western blot. Our study demonstrated that PE could effectively improve the symptoms of asthmatic rats, ameliorate the lung pathological injury, inhibit inflammation, apoptosis and oxidative stress, regulate the levels of macrophages, neutrophils, DCs, NK, Thc, Treg and Th17 cells. PE could collectively inhibit the inflammation, apoptosis and ROS in asthma rats induced by OVA via regulating Th1/Th2 and Th17/Treg cell immune imbalance. [Display omitted] • This paper is the first to explore the intervention effect and mechanism of polysaccharides in Ephedrae Herba on OVA-induced allergic asthma. • Ephedrae Herba polysaccharides may treat OVA-induced allergic asthma by modulating inflammation and immunity. [ABSTRACT FROM AUTHOR]

• We first described the S.maltophilia immunosuppressive effect on T cells and it is meaningful for immunosuppressed patients or co-infections. • T cells stimulated by S.maltophilia with CD4 and CD8 degraded via PD-1/PD-L1 pathway, which led to the massive apoptosis of T cells. • T cells were stimulated by S. maltophilia to secrete IFN-γ. Blocking the PD-1/PD-L1 pathway, apoptosis was suppressed. • S.maltophilia down-regulates host immunity by inhibiting immune cells. Smalotrophomonas maltophilia (S. maltophilia) is common in nosocomial infections. However, few studies have revealed the effect of S. maltophilia on cellular immunity in the host's immune system up to now. In clinical work, we accidentally discovered that S. maltophilia directly stimulated T cells to secrete IFN-γ. S. maltophilia was co-cultured with PBMCs to detect secretion of cytokines (IFN-γ, TNF-α and IL-2) and expression of cell surface molecules (CD3, CD4, CD8, CD69, CD147 and CD152) of T cells. We used light microscopy and electron microscopy to observe the cell morphology and subcellular structure of S. maltophilia co-cultured with lymphocytes. Flow cytometry and Western Blot were used to detect the expression of PD-1/PD-L1 and annexin V in cells. T cells stimulated by S. maltophilia secreted a large amount of IL-2, IFN-γ, and TNF-α. The expression of CD4 and CD8 on the cell surface were declined, accompanied by the activation of the PD-1/PD-L1 pathway, which eventually led to the massive apoptosis of T cells. Electron microscopy showed that cells showed significant apoptotic morphology. Blocking the PD-1/PD-L1 pathway can inhibit the apoptosis-inducing effect of S. maltophilia on T cells. These indicates that T cells are inhibited after being stimulated by S. maltophilia , and then accelerated to induce death without the initiation of an immunologic cascade. This paper demonstrates for the first time the inhibitory effect of S. maltophilia on cellular immunity, and the immunosuppressive effect induced by infection of S. maltophilia should be considered. [ABSTRACT FROM AUTHOR]

Highlights • Few paper investigates the role of CD8+CD28+ T cells in patients with AMI. • The frequency of CD8+CD28+ T cells in patients with AMI were significant increased. • In patients with AMI, frequency of CD8+CD28+ T cells was positively correlated with TNI and negatively associated with LVEF. • The CD8+ CD28+ T cell might participate in the process of myocardial damage. Abstract CD8+ T cells accumulate in the necrotic myocardium of acute myocardial infarction (AMI). It is unclear whether CD8+CD28+ T cells, a specific subset of CD8+ T cells, contribute to myocardial injury. In this study, 92 consecutive patients with AMI and 28 healthy control subjects were enrolled. The frequency of CD8+CD28+ T cells in peripheral blood samples was assayed by flow cytometry. Plasma cardiac troponin I (TNI) and left ventricular ejection fraction (LVEF) were determined. Long-term prognosis of the patients was evaluated by major adverse cardiac and cerebrovascular events (MACCE) over a 12-month follow-up period. Our findings indicated that patients with AMI who presented with high numbers of CD8+CD28+ T cells had an increased infarction size and aggravated ventricular function. We proposed that cytotoxic CD8+CD28+ T cell-mediated myocardial necrosis may act as a novel and alternative pathway of AMI. [ABSTRACT FROM AUTHOR]

T and B lymphocytes are closely related to immunization and pathogen infection. Our previous study confirmed the CD3 + , CD4-1 + , CD4-2 + , CD8β + T lymphocytes and IgM + B lymphocytes presented in the peripheral blood leukocytes (PBLs) of flounder ( Paralichthys olivaceus ), in this paper, the variations of T and B lymphocytes of flounder after Hirame novirhabdovirus (HIRRV) infection or immunization were investigated. The flounders were injected with live or inactivated HIRRV, then the percentages of T and B lymphocytes in PBLs were analyzed by Flow cytometry (FCM), total antibodies and HIRRV-specific antibodies in serum were detected by Enzyme-linked immunosorbent assay (ELISA), and expression of twelve immune-related genes in the head kidneys were determined using q-PCR. The results showed that the percentages of CD3 + , CD4-1 + , CD4-2 + , CD8β + T lymphocytes and IgM + B lymphocytes significantly increased in both infection and immunization groups, in infection group they decreased rapidly after the peak and significantly lower than control levels at the end of infection, in immunization group they went down steadily to the control levels at the end of immunization. The total antibodies and HIRRV-specific antibodies increased first and peaked on the 7 th day post infection and on the 14 th day post immunization, respectively, then gradually decreased to the control levels. Additionally, twelve immune-related genes were up-regulated in both groups. These results demonstrated that the HIRRV induced both humoral and cellular immunity of flounder, the lymphocytes varied more sharply in infection group than those in immunization group and CD8 + T lymphocytes responded much more than CD4 + T lymphocytes to HIRRV antigen. [ABSTRACT FROM AUTHOR]

In the previous study, antibodies against CD3 molecule have been produced and were used in labeling T cells in Japanese flounder ( Paralichthys olivaceus ). In this paper, CD4 + and CD8 + lymphocytes subpopulations in peripheral blood leucocytes (PBL), spleen and head kidney of flounder were investigated. The flounder CD4-1, CD4-2 and CD8β recombinant proteins and their antibodies (Abs) were produced, then the cross-reactivity of the Abs to CD4-1, CD4-2 and CD8β was detected by Western blotting, respectively, and the reactions of Abs to PBL were analyzed by immunofluorescence staining (IFS) and flow cytometry (FCM). CD4-1 + /CD3 + , CD4-2 + /CD3 + , and CD8β + /CD3 + lymphocytes in PBL, spleen and head kidney were observed by double IFS, then their proportions were analyzed using two-color FCM, respectively. Further, CD4-1/CD8β, CD4-2/CD8β, or CD4-1/CD4-2 lymphocytes were analyzed using double-IFS and two-color FCM. Finally, CD4-1 + , CD4-2 + , and CD8β + lymphocytes in spleen and head kidney were observed by immunohistochemistry. The results showed that the Abs were specific for CD4-1, CD4-2 and CD8β molecules, respectively. The proportions of CD4-1 + /CD3 + , CD4-2 + /CD3 + , and CD8β + /CD3 + lymphocytes were 6.7 ± 2.0%, 8.6 ± 2.8%, 2.1 ± 1.3% in PBL; 13.6 ± 3.6%, 15.6 ± 5.2%, 2.8 ± 1.4% in spleen; 20.0 ± 4.6%, 20.5 ± 4.6%, 3.2 ± 1.5% in head kidney, respectively. Most CD4 + and CD8 + cell subpopulations belonged to CD3 + cells; there were no cross-reactivity between CD4 + and CD8 + cells. CD4-1 + /CD4-2 − , CD4-1 − /CD4-2 + , and CD4-1 + /CD4-2 + cells presented different proportions in PBL, spleen and head kidney, among them, CD4-1 + /CD4-2 + cell is the majority of CD4T cell subpopulation. [ABSTRACT FROM AUTHOR]

T cell response is crucial to the pathogenesis and progression of rheumatoid arthritis (RA). IL-7/IL-7R axis has significant effect on CD4 + T cell response, including proliferation, differentiation, survival and migration. However, whether blockade of IL-7/IL-7R axis signaling can relieve RA and what is the potential treatment mechanisms are still remaining unclear. In this paper, we established collagen-induced arthritis (CIA) model and observed the effect of IL-7Rα antibody in the treatment of CIA mice. It is demonstrated that IL-7Rα antibody significantly alleviated clinical symptoms of CIA mice, accompanied with reduced CD4 + T cell number in both spleen and joints. Decreased CII-specific CD4 + T cell proliferation and reduced mRNA expression of inflammatory cytokines in IL-7Rα antibody-treated mice were observed. Subsequently, IL-7Rα antibody treatment in vivo downregulated the percentages of Th1 and Th17 cells and the mRNA expression of T-bet and RORγt gene. Moreover, it was found that IL-7 promoted Th1 cell differentiation in vitro, while having no effect on Th17 cell differentiation. In addition, administration of IL-7Rα antibody reduced the mRNA expression of chemokine receptors (CCR7, CXCR3, CXCR6 and XCR1) on CD4 + T cells and chemokine CXCL2 in joints. The results suggested that IL-7Rα antibody treated CIA mice via the inhibition of CII-specific CD4 + T cell proliferation, the reduction of Th1 cell differentiation and the restrain of CD4 + T cell migration to joint lesion site. This investigation indicates that IL-7Rα is a potential therapeutic target for RA. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports the cloning and sequencing of interleukin (IL)-23 p19 subunit for the first time within a non-mammalian species, the zebrafish (Danio rerio), which was discovered using a synteny approach. In addition, amino acid sequences were for IL-23 p19 subunits were also predicted from the stickleback, Fugu and Tetraodon genomes and included in this investigation. The zebrafish IL-23 p19 cDNA consisted of a 66bp 5′ UTR, a 249bp 3′ UTR and a single open reading frame of 567bp giving a predicted 188 aa IL-23 p19 molecule. Multiple alignment of zebrafish IL-23 p19, with other known IL-23 p19 and IL-12 p35 amino acid sequences revealed areas of amino acid conservation, such as the presence of four predicted α-helixes, cysteines important for disulphide bond formation and the conservation of a tryptophan known to interact with the receptor. Amino acid homologies and phylogenetic analysis confirmed the relationship of the fish IL-23 p19 subunits with their mammalian homologues. All the teleost fish IL-23 p19 subunits were found to have 4 exons and 3 introns similar to that of human and mouse IL-23 p19 and a limited degree of synteny was found between the organisms for the regions containing the IL-23 p19 genes with only PAB-dependent poly(A)-specific ribonuclease subunit 2 (PAN2) and IL-23 p19 found in the same order on human chromosome 12 and all the fish genomes looked at. Lastly using real-time PCR, constitutive expression of IL-12 p40 and IL-23 p19 was observed in the kidney, liver, gut and muscle with IL-12 p40 expression higher than IL-23 p19. As soon as an hour after stimulation with LPS, there was an increase of IL-23 p19 in zebrafish leukocytes and an increase of IL-1β, IL-12 p40 and IL-23 p19 expression was found after infection of zebrafish for 1 or 6 days with Mycobaterium marinum strain E11. [Copyright &y& Elsevier]

Abstract: Withanolide, coagulin-H (1), was evaluated for its effect on various cellular functions related to immune response including lymphocyte proliferation, and expression of interleukin-2 (IL-2) cytokine, and results were compared with prednisolone (2), a commonly used immune modulating drug. Coagulin-H (1) was found to have a powerful inhibitory effect on lymphocyte proliferation and Th-1 cytokine production. Inhibition of the phytohaemagglutinin (PHA)-activated T-cell proliferation by coagulin-H (1) was observed in a concentration dependant manner. A complete suppression of PHA-activated T-cell was observed at ≥2.5μg/mL concentrations of compound (1) and this suppression activity was similar to that of prednisolone (2). Coagulin-H (1) also significantly inhibited IL-2 production by 80%. The interactions of coagulin-H (1) (a natural inhibitor) and prednisolone (2) (a drug) to IL-2 were also investigated in order to understand the differences in their effects on T-cell responses. This paper also describes the results of molecular docking study on IL-2 inhibition. Docking studies predicted that coagulin-H (1) binds to receptor binding site of IL-2 more effectively than prednisolone (2). Based on the computational and the experimental results, coagulin-H (1) was identified as a potential immunosuppressive candidate. [Copyright &y& Elsevier]

T-cells provide antigen specific focus to the adaptive immune response. However, the receptors that initiate functional responses are not in themselves specific, as they can recognise many different ligands. In this paper, we propose that the immune system deals with TCR degeneracy by an adaptive process that effects both T-cell activation and T-cell function, and exploits TCR degeneracy to limit pathogenic autoimmune disease. [Copyright &y& Elsevier]

This paper discusses some consequences of the discovery that antigen receptors are degenerate: Immune specificity, in contrast to the tenets of the clonal selection paradigm, must be generated by the immune response down-stream of initial antigen recognition; and specificity is a property of a collective of cells and not of single clones. [Copyright &y& Elsevier]