The Study Of The Activated T Lymphocytes By Myosin Induced Myocardial Inflammation And Remodeling After Transfer

PartⅠMyocardial autoimmune response induced by transferring myosin-activated T lymphocytes in ratsObjective: The autoimmune response was initiated by cardiac myosin which is an autoantigen. The myosin was released and autoantibody was produced after acute myocardial infarction (AMI). The present study was to investigate the myocardial autoimmune response which was induced by transferring myosin-activated T lymphocytes adoptively in AMI.Method: T lymphocytes and dendritic cells were respectively purified from spleens of Lewis rats. After co-culturing in the absence or presence of cardiac myosin (20μg/ml), sensitized or unsensitized T lymphocytes were transferred into na?ve syngeneic Lewis rats by a single tail vein infusion, respectively. These recipient rats were separately killed at the 3rd day, 1st, 4th and 8th weekend, and histopathology and echocardiography were performed.Result: T lymphocytes infiltration was observed in the 3rd day and the most markedly and occasional myocardium necrosis at the 1st weekend. The infiltration distinctly lessened at the 4th weekend and not detected at the 8th weeks. No cellular infiltration was found in multiple sections of the kidney, liver, lung, and brain. T cell infiltration was not detected in the heart sections of the rats of transferred with unsensitized T lymphocytes. Marked LV dilatation and LV systolic dysfunction could not be ascertained by echocardiography in the group received activated T lymphocytes. Conclusion: Myocardial autoimmune response after AMI could be induced by myosin-activated T lymphocytes.PartⅡThe expression of myocardial cytokines induced by myosin-activated T lymphocytes in transferred ratsObjective: The autoimmune response was initiated by cardiac myosin which is an autoantigen. The myosin was released and autoantibody was produced after acute myocardial infarction (AMI). The present study to investigate the expression of myocardial cytokines in rats adoptively trandferred with myosin-activated T cells.Methods:T lymphocytes and dendritic cells were respectively purified from spleens of Lewis rats. After co-culturing in the absence or presence of cardiac myosin (20μg/ml), sensitized or unsensitized T lymphocytes were transferred into na?ve s yngeneic Lewis rats by a single tail vein infusion, respectively. Recipient rats were separately killed at the 3rd day, 1st, 4th and 8th weekend after transfer to perform histopathological and hemodynamics study. In addition, mRNA and protein expression of interleukin-1β(IL-1β), IL-6, tumor necrosis factor (TNF)-αand IL-10 in myocardial tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry respectively.Results:T lymphocytes infiltration and occasional myocardium necrosis were observed in the rats after transferred with activated T cells, the most markedly at the 1st weekend and not detected in the rats receiving unactivated T cells. LV pressure maximal rate of rise and fall (+/-dp/dtmax) were found decreasing by the hemodynamics monitor (P<0.05) at the end of the 4th and 8th week after received activated T cells. IL-1β, IL-6, TNF-αand IL-10 were detected at the 3rd days, the mRNA and protein expression were elevated markedly at 1 week and decreased at the 4th week, and then resumed approach baseline at the 8th week. Conclusion: Myocardial inflammatory response and expression of pro-inflammatory cytokines after AMI might be mediated by myosin-activated T lymphocytes.PartⅢThe expression of genes involved in remodeling mediated by myosin-activated T lymphocytes in transferred ratsObjective: The autoimmune response was initiated by cardiac myosin which is an autoantigen. The myosin was released and autoantibody was produced after acute myocardial infarction (AMI). The present study was to investigate the expression of genes involved in remodeling in rats which was adoptively transferred with myosin-activated T cells.Methods:T lymphocytes and dendritic cells were respectively purified from spleens of Lewis rats. After co-culturing in the absence or presence of cardiac myosin (20μg/ml), sensitized or unsensitized T lymphocytes were transferred into na?ve syngeneic Lewis rats by a single tail vein infusion, respectively. Recipient rats were separately killed at the 3 day, 1st, 4th and 8th weekend after activated T cells transfusion to perform histopathological and hemodynamics studies. Apoptosis of heart be detected by TUNEL. With RT-PCR, we evaluated the expression of matrix metalloproteinase (MMP)-2, tissue matrix metalloproteinase inhibitor (TIMP)-2 mRNA and myocardial fetal gene (myosin heavy chain:α,β-MHC).Results:T lymphocytes infiltration and occasional myocardium necrosis were observed in the rats transferred with activated T cells, the most markedly at the 1st weekend but not detected in the rats of received unactivated T cells. At the 4th and 8th weekend, blue apoptotic bodies can be found in cardiac myocytes. The expression of the myocardial fetal gene changed differently:α-MHC evidently decreased at the 4th and 8th weekend whileβ-MHC increased. The levels of MMP-2 increased at the 1st and 4th weekend while that of TIMP-2 at the 4th and 8th weekend.Conclusion: The expression of genes involved in remodeling was mediated by myosin-activated T lymphocytes.