| Myasthenia Gravis (MG) is an autoimmune disease, characterized by striated muscles fatigue. Antibodies to the nicotinic acetylcholine recepter (AChRab) were reported increased in blood of patients, and to cause loss of AChRs at the synapse memberance and impair acetylcholine competitively. But the ditails of autoreactive antibody producing and initial mechanism of autoimmunity are still uncertain. Evidences of abnormal thymus in MG patients were reported in recent years, it is reasonable to suspect that an abnormal thymus may play an important role in the initiation and progresing of autoimmune. Previous studies show that there were small amount of thymic myoid cells and dendritic cell ( thymic dendritic cells, TDC) in the normal thymus, but they are increased in the cortial-medulla junction of MG thymus surrounded with germinal centers (GCs), which provid a structure relation for autoimmune initiation. It is known that in thymic myoid cells the componets of AChR are highly exprssed and translated, which have the same mRNA with AChR from synapse. The thymic dendritic cells (TDCs) are the nature antigen-presenting cells (APC), Why they proliferate actively in MG thymus? And are the activated TDCs participate in the processing of MG? And could the activated TDCs present antigen AChR especially in MG thymus? The answers to these questions will reveal the roles of TDCs in the progressing of MG autoimmune and clarificate the mechanisms. Accordingly, some agents, which inhibit the activation of TDC, should be found to prevent and cure the disease. This objects are designed on the basis of previous studies, and carried out in 5 aspects described as below: (1) To establish the method of primary culture of TDC in vitro and observe the influence on the growth of TDC by cytokines. (2) To study the activity of TDCs in pathologically different MG thymus, and to compare the expression of surface and costumulating moleculs of TDCs in normal and MG thymus; (3) To study the expression of IL-12, IFN-γand their mRNA during the procession of the TDCs differenciation through ELISA and RT-PCR; (4) To examine the effection of TDCs on AChR-association activeted lymphocytes through mixed lymphocyte reacion, in order to reveal the relationship of AChR with AChR-association activeted lymphocytes in MG thymus; (5) To explore the effects of IL-10 on antigen-presenting of TDCs through mixed colture of TDCs and IL-10; (6) To observe the association of TDCs proliferation and ability of antigen-presenting, titers of AChR in serum with the clinical effects through antibody examination and clinical follow-up.The main results and conclusion:1. TDCs produced from induced pre-TDC by GM-CSF and SCF, which collected by procedures of breaking, filtering, centrifugation from hyperplastic thymus with MG. The proliferation of TDCs was changed with different pathologic thymus, and the changes were obvious in hyperplastic thymus, followed by atrophy and thymoma, which were significant than normal thymus TDCs.2. During the mature processing of DC in MG thymus, the expression of immumo-adhesive molecules HLA-DR, CD11c, CD80, CD86, CD40 and CD54 were higher than TDCs in normal thymus; the concentration of IL-12, INF-γ in serum and their mRNA in TDC were also higher than that in normal thymus; the mature TDCs in MG thymus had higher capability to stumulate TB-2. The results indicate that MG TDCs could present the special antigen AChR; while TDCs though could be seen in normal thymus was scanty and could not stimulate TB-2. 3. The function of TDCs was different in different MG thymus. The facts, that adhesive molecules CD11c was expressed 63.14% on TDC from MG hperplasia thymus, and that other molecules described above were apparently higher in hyperplasia thymus than atrophy and thymoma, revealed that TDCs in hyperplasis thymus had the most activities.4. When cultured with IL-10, the activities of TDCs from different MG thymus were decreased.This may indicate that IL-10 could inhibit TDCs presenting antigen AChR, and might be used to prevent... |
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