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Article in English | WPRIM | ID: wpr-225154


In Trichinella spiralis infection, type 2 helper T (Th2) cell-related and regulatory T (T(reg)) cell-related immune responses are the most important immune events. In order to clarify which Toll-like receptors (TLRs) are closely associated with these responses, we analyzed the expression of mouse TLR genes in the small intestine and muscle tissue during T. spiralis infection. In addition, the expression of several chemokine- and cytokine-encoding genes, which are related to Th2 and T(reg) cell mediated immune responses, were analyzed in mouse embryonic fibroblasts (MEFs) isolated from myeloid differentiation factor 88 (MyD88)/TIR-associated proteins (TIRAP) and Toll receptor-associated activator of interferons (TRIF) adapter protein deficient and wild type (WT) mice. The results showed significantly increased TLR4 and TLR9 gene expression in the small intestine after 2 weeks of T. spiralis infection. In the muscle, TLR1, TLR2, TLR5, and TLR9 gene expression significantly increased after 4 weeks of infection. Only the expression of the TLR4 and TLR9 genes was significantly elevated in WT MEF cells after treatment with excretory-secretory (ES) proteins. Gene expression for Th2 chemokine genes were highly enhanced by ES proteins in WT MEF cells, while this elevation was slightly reduced in MyD88/TIRAP-/- MEF cells, and quite substantially decreased in TRIF-/- MEF cells. In contrast, IL-10 and TGF-beta expression levels were not elevated in MyD88/TIRAP-/- MEF cells. In conclusion, we suggest that TLR4 and TLR9 might be closely linked to Th2 cell and T(reg) cell mediated immune responses, although additional data are needed to convincingly prove this observation.

Animals , Gene Expression , Humans , Interleukin-10/genetics , Mice , Mice, Knockout , Th2 Cells/metabolism , Toll-Like Receptors/genetics , Trichinella spiralis/genetics , Trichinellosis/genetics
Article in English | WPRIM | ID: wpr-78169


We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific IgE and IgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-alpha (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.

Administration, Intranasal , Animals , Anisakiasis/immunology , Anisakis/immunology , Bronchoalveolar Lavage Fluid , Chemokines/metabolism , Cytokines/analysis , Eosinophils/metabolism , Female , Gene Expression Regulation/immunology , Helminth Proteins/immunology , Hypersensitivity/immunology , Immunoglobulin E/immunology , Immunoglobulin G/immunology , Larva/immunology , Lung/metabolism , Mice , Mice, Inbred C57BL , Recombinant Proteins/immunology , Th17 Cells/metabolism , Th2 Cells/metabolism
Article in English | WPRIM | ID: wpr-181122


Regulatory T cells, which stimulate or inhibit the effector functions of distinct T cell subsets, are critical in the control of the immune response. We investigated the effect of TGF-beta and IL-10 on T cell subsets according to the Th1/Th2 immune status. Sixty-two patients with asthma and 38 patients with pulmonary tuberculosis were included. Allergy skin tests, tuberculin tests, and chest radiography were performed. The levels of circulating IL-4, IFN-gamma, TGF-beta1, and IL-10 were measured using ELISA. The level of TGF-beta1 was higher in patients with asthma than in those with tuberculosis, but the IL-10 levels were the same between the asthma and tuberculosis groups. Atopy was unrelated to the tuberculin response. The IFN-gamma level was correlated with the IL-10 level, and the level of IL-4 was unrelated to the IL-10 or TGF-beta1 level. The level of IL-10 was higher in the negative tuberculin reactors than in the positive tuberculin reactors among patients with asthma, and TGF-beta1 was higher in the positive tuberculin reactors than in the negative tuberculin reactors among patients with tuberculosis. These results demonstrate that the regulatory effects of circulating TGF-beta and IL-10 on T cell cytokines may be different between Th2-type asthma and Th1 tuberculosis.

Adult , Asthma/blood , Cytokines/blood , Female , Humans , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-4/blood , Male , Respiratory Function Tests , Skin Tests , Th1 Cells/metabolism , Th2 Cells/metabolism , Transforming Growth Factor beta/blood , Tuberculin Test , Tuberculosis/blood
Mem. Inst. Oswaldo Cruz ; 96(suppl): 89-101, Sept. 2001. ilus, graf, tab
Article in English | LILACS | ID: lil-295895


T cell clones were derived from peripheral blood mononuclear cells of Schistosoma haematobium infected and uninfected individuals living in an endemic area. The clones were stimulated with S. haematobium worm and egg antigens and purified protein derivative. Attempts were made to classify the T cell clones according to production of the cytokines IL-4, IL-5 and IFN-gamma. All the T cell clones derived were observed to produce cytokines used as markers for the classification of Th1/Th2 subsets. However, the 'signature' cytokines marking each subset were produced at different levels. The classification depended on the dominating cytokine type, which was having either Th0/1 or Th0/2 subsets. The results indicated that no distinct cytokine profiles for polarisation of Th1/Th2 subsets were detected in these S. haematobium infected humans. The balance in the profiles of cytokines marking each subset were related to infection and re-infection status after treatment with praziquantel. In the present study, as judged by the changes in infection status with time, the T cell responses appeared to be less stable and more dynamic, suggesting that small quantitative changes in the balance of the cytokines response could result in either susceptibility or resistant to S. haematobium infection

Humans , Animals , Child , Cytokines/biosynthesis , Schistosoma haematobium/immunology , Schistosomiasis haematobia/immunology , T-Lymphocytes, Helper-Inducer/classification , Anthelmintics/therapeutic use , Antigens, Helminth , Cell Line , Clone Cells/classification , Clone Cells/metabolism , Cytokines/analysis , Cytokines/isolation & purification , Enzyme-Linked Immunosorbent Assay , Follow-Up Studies , Parasite Egg Count , Praziquantel/therapeutic use , Schistosomiasis haematobia/drug therapy , T-Lymphocyte Subsets/classification , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Helper-Inducer/metabolism , Th1 Cells/classification , Th1 Cells/metabolism , Th2 Cells/classification , Th2 Cells/metabolism , Titrimetry