Analysis of clinical data and T helper 1/T helper 2 responses in patients with different clinical forms of leprosy

Abstract INTRODUCTION: Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. METHODS: Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. RESULTS: The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). CONCLUSIONS: The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.

A murine model of Th2 response induced by shrimp tropomyosin / 中国免疫学杂志

Objective:To develop murine models of Th2 response induced by shrimp tropomyosin (ST). Methods:Mice were sensitized with ST for 6 weeks. The serum antigen-special IgE (sIgE),total IgE and sIgG level,Th1/Th2 cytokines production were measured by ELISA. The basophil activation in mice was measured by flow cytometry. Results:The intraperitoneal sensitization with ST for 6 weeks induced significant increase of serum sIgE,total IgE and sIgG (sIgG1,sIgG2a and sIgG2b) level in mice. Th2 cell response was induced and cytokines (IL-4,IL-5,IL-10 and IL-13) production increased in splenocytes stimulated by ST,while Th1 cytokine (IFN-γ) production decreased. As the markers of basophil activation,CD200R and CD41 expression also increased in response to ST. Conclusion:The Th2 response is dominant in ST-induced anaphylaxis in mice.

The effects of intestinal nematode infection on experimental periodontitis in mice / 实用口腔医学杂志

Objective: To investigate the effect of polarizing the immune response toward the Th2 type, using intestinal nematode (Trichinella spiralis) infection, on subsequent experimental periodontitis. Methods:Thirty six SPF KM mice were randomly divided into three groups. Periodontitis group: experimental periodontitis was induced by wrapping a 5/0 silk ligature inoculated with putative periodontopathic bacteria around the first maxillary molar. Th2-polaried group: After the mice were infected with low dosage Trichinella spiralis, the experimental periodontitis model was established at that time as above. Mice were sacrificed at the end of 1, 4, 8, 12 weeks. The histological analysis of periodontal tissues was observed by microscope after the samples were stained with hematoxylin and eosin (H&E). The concentrations of IFN--y and IL-4 in mouse serum were determined by ELISA. Results; The results showed that compared with control group Th2-polaried mice had high levels of IL-4 prior nematode infection reduced the severity of periodontitis, and subsequent infection of the periodontium with oral pathogens developed minimal lesions. Few or no osteoclasts were detected in lesions of Th2-polaried group. Conclusion;These results indicate a protective role of nematode infection in Thl cell-driven periodontal damage and prompt consideration of a novel therapeutic strategy in periodontitis based on im-munological distraction.

The roles of thymic stromal lymphopoietin receptor and its antibody in airway inflammatory response in asthmatic mice / 中华微生物学和免疫学杂志

Objective To determine the roles of thymic stromal lymphopoietin receptor (TSLPR) and its antibody in airway inflammatory response in asthmatic mice, and to promote maturation and activation of dendritic cells (DCs) in mouse airway. Methods BALB/c mice were randomly divided into group A, B and C. The mice in group B and C were intraperitoneally injected with OVA for allergization while the mice in group A were intraperitoneally injected with PBS as the normal control. The mice in group B and C were treated by inhalation of non-specific IgG and TSLPR IgG respectively, before provocation of asthma using OVA. The bronchoalveolar lavage fluid (BALF) of the mice in different groups were collected for cell differential counts and quantitative detection of IL-4, IL-5, IFN-γand IL-10 levels by ELISA. Moreover, the pulmonary tissue specimens of the mice were collected for pathological examination, and the numbers and phenotypes of DCs from the local lymph nodes and pulmonary tissue were determined by flow cytometry. Results The levels of all the tested cytokines in the BALF from mice in group B and C were remarkably higher compared to those from mice in group A (P<0.01). However, both the IL-4 and IL-5 levels in the BALF from group C mice that pre-blocked with TSLPR IgG were lower than those from group B (P<0.05, P<0.01), whereas both the IFN-γ and IL-10 levels in the BALF from group C mice were higher than those from group B (P<0.05, P<0.01). Furthermore, the numbers of total cells, eosinophils and lymphocytes in the BALF from group C mice were also lower than those from group B (P<0.01). A large number of inflammatory cell infiltration around the bronchus, beaker cell proliferation and mucous secretion reinforcement could be found in the samples from group B mice, while slight inflammatory cell infiltration and beaker cell proliferation in the samples from group C mice. The numbers of DCs in mediastinal lymph node and the levels of I-Ad, CD40, CD80 and CD86 expression of pulmonary DCs from group B mice were higher than those from group C mice (P<0.05). Conclusion TSLP/TSLPR have an effect on promoting asthma, which is closely relative to its regulation of DCs activation. And the interference of TSLPR antibody can decrease the effect of TSLP/TSLPR which indicating a potential of the antibody as a novel anti-asthma drug.

Cytokine and antibody responses of reactivated murine toxoplasmosis upon administration of dexamathasone

Toxoplasma gondii has been shown to result in life-threatening encephalitis in immunocompromised patients after reactivation of dormant parasites. In order to obtain information on immune responses related to this phenomenon, BALB/c mice were infected with 25 cysts of the 76K strain of T. gondii, then, treated orally with dexamethasone (Toxo/Dexa-treated group) in order to reactivate the chronic toxoplasmosis. None of the T. gondii-infected mice died during the experimental periods, whereas the Toxo/Dexa-treated mice evidenced a significant attenuation of survival periods. Toxoplasma-specific IgG2a, IgA and IgM titers in sera were significantly depressed in the Toxo/Dexa-treated mice; however, the IgG1 sera titers were similar to those seen in the Toxoplasma-infected mice. The percentages of CD4+ and CD8 alpha + T cells in the Toxo/Dexa-treated mice were significantly reduced 2 weeks after dexamethasone treatment. IFN-gamma and IL-10 production levels in the Toxo/Dexa-treated mice were depressed significantly, whereas IL-4 production was increased temporarily. The expression levels of the Toxoplasma-specific P30 and B1 genes were found to have been increased in the Toxo/Dexa-treated mice in comparison with the Toxoplasmainfected mice. Collectively, the findings of this study demonstrate that reactivation of murine toxoplasmosis as the result of dexamethasone treatment induced a depression in Th1 immune responses, whereas Th2 immune responses were not significantly influenced.

Repeated Ozone Exposure Induces Th2 Immune Responses in Mice

BACKGROUND AND OBJECTIVES: It has been reported that ozone exposure exacerbate allergic rhinitis symptoms and may contribute to increase allergic rhinitis prevalence. However, a causal relationship still remained unsolved. The purpose of this study is to investigate whether prolonged exposure to ozone induce Th2 immune response without allergen. MATERIALS AND METHODS: Fourteen BALB/c mice were divided into two groups: control group and ozone exposure group. Mice were exposed to 0.3 ppm of ozone for 4 hours a day, 3 times per week, for 4 weeks. At 24 hour after the last ozone exposure, nasal lavage fluid (NLF) was obtained to measure the levels of cytokine IL-4, IL-5, and IFN-gamma. After lavage fluid was obtained, blood was obtained via inferior vena cava to measure the amount of total IgE and IgG1. The concentration of cytokines and immunoglobulins was measured using the ELISA method. In addition, Luna staining was performed to identify eosinophils infiltrated in nasal mucosa. RESULTS: The levels of IL-4 and IL-5 in NLF were significantly increased in ozone exposure group compared with control group. But the level of IFN-gamma in NLF shows no significant difference between two groups. Serum total IgE and IgG1 were significantly increased in ozone exposure group compared with control group. On histologic examination, number of eosinophils infiltrating nasal mucosa was significantly increased in ozone exposure group. CONCLUSION: These results suggest that repeated ozone exposure induces Th2 response in the nasal mucosa of mice.

Concurrent Impairment of Th1 and Th2 Response in Thermal Injury

Large numbers of reports have shown that thermal injury (TI) causes a wide spectrum of defects in immune response that lead to a high susceptibility to various opportunistic infections. However, it is still a matter of debate whether TI induces Th2 polarization or global impairment in Th1/Th2 response. In this study, TI in a mouse model was induced by exposing shaved dorsal skin to boiling water and cytokine production was analyzed. At day 2 of injury, whole spleen cells and T cells were collected and then stimulated with an anti-CD3 antibody. The levels of cytokine secretion were determined by cytokine ELISA. Production of IFNgamma and IL 4 by whole spleen cells from injured mice were concurrently decreased when compared to those from sham-injured controls. Proportional changes in T, B, and T-subset cells were not accompanied. Using purified T cells devoid of accessory cells (AC), it was shown that those defects resulted primarily from lowered T cell potentials. By using mixed cultures of sham T and TI-AC and vice versa, it was revealed that AC also acted as inhibitor cells in IFNgamma and IL 4 production in less extent. Blockade of glucocorticoid signals rendered the T cells partially resistant to TI-induced inhibition in IFNgamma and but not IL 4 production. These results clearly demonstrate that TI induces overall suppression in Th1 and Th2 response through T cell dysfunction together with the inhibition of AC activity, and that reduction in only IFNgamma but not IL 4, production may be caused, in part, by corticosteroid hormone that is secreted prominently during trauma.

A Study on Dermatophagoides pteronyssinus Induced Cytokines Gene Expression in Peripheral Blood Mononuclear Cells / 소아알레르기및호흡기학회지

PURPOSE: Cytokines are known to play a major role in mediating many of the immunological and pathological findings of allergic disease. Many studies on allergen-specific T cell clones isolated from atopic individuals have shown that these cells produce cytokines of the Th2 phenotype. The purpose of the present study was to investigate cytokine patterns of T lymphocyte induced by Dermatophagoides pteronyssinus in atopic asthma. METHODS: Freshly isolated peripheral blood mononuclear cells of Dp(+) asthmatic children, Dp(-) asthmatic children, nonasthmatic children, and normal adults were stimulated with Dp antigen and examined for the induction of IFN-gamma, IL-2, IL-4, and IL-5 mRNA using RT-PCR. RESULTS: The lymphoproliferative response to crude Dp antigen was maximized at Dp concentration of 2.5 microgram/mL. The lymphoproliferative response was low in children including Dp(+) asthmatics, Dp(-) asthmatics and nonasthmatics, but that of normal adults was high. The expression of IFN-gamma was not so different in each group, but the expression of IL-4 was least in adults, and that of IL-5 was most prominent in Dp(+) asthmatic children. In adult healthy group, IFN-gamma expression without IL-4 and IFN-gamma without IL-5 was significantly higher than those in children. IL-5 expression with or without IFN-gamma was the highest in Dp(+) asthmatic children. IL-4 and IL-5 or IL-5 without IL-4 expression were observed more frequently in Dp(+) asthmatic children than in any other groups. Th2 response was most prominent in Dp(+) asthmatics, and Th1 response was most prominent in normal adult group. CONCLUSION: In conclusion, we observed significantly prominent Th2 response in Dp(+) asthmatic children, especially that of IL-5.

Dendritic Cells and Th2 Response Induced by Schistosome Infection / 中国寄生虫学与寄生虫病杂志

Dendritic cells act as the major antigen presenting cells in the body and play a central role in intri-guing the adaptive immune response. Protective immunity against schistosome and immuno-pathological response in host caused by eggs are both closely associated with Th2 response. Further understanding on immune mechanism will contribute to the development of vaccines against schistosome infection, as well as the relief of the pathological lesion in schistosomiasis. This article discusses the central role of dendritic cells in the mechanism of Th2 response induced by schistosome (including eggs).