Mechanism Of Specific Immunotherapy In The Treatment Of Asthma

With the development of methodology, specific immunotherapy with allergen was extensively applied in the treatment of allergic asthma. Increasing clinical data have shown that specific immunotherapy could ameliorate lung function, decrease airway hyper reactivity (AHR) to specific allergen and decrease the used drugs for controlling asthma. However, specific immunotherapy could not completely eliminate the symptoms of asthma, as well as could cause systemic/local response. Therefore, clinical curative effect and security of specific immunotherapy should be guarantied before it is extensively used in clinic all over the world. Most important cause for limited curative effect and security contribute to the little knowledge of the mechanism by which specific immunotherapy treat allergic asthma SIT. Therefore, to thoroughly explore the mechanism by which specific treat asthma is of great significance to increase the curative effect and security, and thoroughly elucidate the pathological mechanisms of asthma. Presently, Many aspects of the immune responses associated with allergic disorders, including antibody production, cytokine secretion, T cell activation and local inflammatory reactions, are found to be significantly altered during and/or after immunotherapy. Specifically, four proposal for interpretation of the mechanism include; (1) induced production of blocking antibodies; (2) modulation of inflammatory mediators; (3) promotion of Th2 to Th1 polarization. (4) induction of peripheral immune tolerance. Of all, promotion of Th2 to Th1 polarization and induction of peripheral immune tolerance were widely accepted and have been become spot in this field. And the mechanisms for peripheral immune tolerance include(1) clonal deletion of T lymphocyte; (2) T cell anergy; (3) immune regulation.Twenty-three asthmatic patients allergic to Dermatophagoides and sixhealthy volunteers were in enrolled in this study. Their clinical parameters, such as asthma symptom scores and FEV1%, were monitored. Moreover, secretion of cytokines from peripheral blood mononuclear cell (PBMC), such as IL-4, IL-10, IL-2 and IFN-γ, were detected by ELISA. Thirdly, 3H-TdR incorperation assay was used to determine the response of PBMC to Dermatophagoides. Our results showed that specific immunotherapy improved clinical indices of disease activity including symptom scores and medication use, and significantly ameliorate FEV1%. Moreover, it had marked effect in decreasing the production of IL-4 and IL-2 in PBMC and specific response to Dermatophagoides, but increasing IL-10. Our present results suggested ①Th2 polarization occurred in the patient with allergic asthma; ②specific immune tolerance were established after specific immunotherapy; ③establishment of immune tolerance induced by specific immunotherapy might contribute to the increase of IL-10. Secondary part of this study was emphasized on the mechanism by which specific immunotherapy induce immune tolerance, through establishing OVA-sensitized mice model for specific immunotherapy. Through present study we found following results: inhalation challenge of the mice with OVA-sensitized and OVA-specific immunotherapy revealed almost complete inhibition of eosinophil infiltration, as well as IL-4 production of mononuclear cells from spleen stimulated with OVA in vitro was largely reduced; the specific response of spleen-derived T cells to OVA and production of IL-4 in these cells were decrease, while IL-10 were significantly increased; CD80 molecule on the surface of spleen-derived dendritic cells were up-regulated, while there was no change in the context of CD86 molecule; CD86 were down-regulated after immunotherapy, while CD80 molecule did not change; CTLA-4 molecule on the surface of T lymphocytes were up-regulated after immunotherapy. Above results suggested that ①up-regulation of CD80 on the surface of dendritic cells might be involved in the pathology of asthma; ②anergy were induced by specific immunotheapy; ③CTLA-4 up-regulated on T cell by specific immunotherap...