Abstract: Objective To assess the feasibility of transferring major histocompatibility complex (MHC) gene into the thymus to mitigate xenograft rejection. Methods By molecular cloning technique, we extracted and proliferated the-H-2K d gene from donor mice (MHC class Ⅰ gene of Balb/c mice) and constructed the expression vector plasmid of pCI-H-2K d. Twenty SD rats were selected as receptors, and by using random number table, they were divided into the experimental group and the control group with equal number of rats in each group. By ultrasoundguided puncture and lipofection method, the pCI-H-2Kd was injected into thymus of SD rats in the experimental group and meanwhile, empty vector plasmid of pCIneo was injected into thymus of SD rats in the control group. Subsequently, we transplanted the donor mice myocardium xenografts into the receptor rats, and observed the xenograft rejection in both the two groups. Results The survival time of the xenotransplanted myocardium in the experimental group was significantly longer than that in the control group (14.61±2.98 d vs. 6.40±1.58 d, t=-7.619,Plt;0.05). Microtome section of transplanted myocardium in the control group showed a relatively large amount of lymphocyte infiltration and necrosis occurred to most part of the transplanted myocardium, while microtome section of experiment group showed no lymphocyte infiltration and most of the cells of the transplanted myocardium were still alive. After mixed lymphocyte culture, the reaction of receptors to donor cells in the experiment group was obviously lower than that in the control group (t=4.758, P=0.000).After the count by flow cytometer, the xenoMHC molecules were expressed in the receptors’ thymus with a transfection efficiency of 60.7%. Conclusion Our findings suggest that xenograft rejection can be mitigated substantially by donor’s MHC gene transferring into receptor’s thymus. This may provide theoretical and experimental evidence for inducing xenotransplantation tolerance.
Thymic neuroendocrine tumors (TNETs) are a series of rare diseases with aggressive biology and poor prognosis. Clinical manifestations of TNETs are atypical, and ectopic secretion of adrenocorticotropic hormone can be found in some cases, resulting in associated endocrine symptoms. Due to the low morbidity and strong heterogeneity, it’s difficult to diagnose, treat and obtain new treatment regimen. Early complete surgical resection is an effective treatment. For advanced cancer, clinical trials of new drugs are expected to improve the survival of patients.
Thymectomy is the main treatment for thymoma and other thymic diseases. But the incidence of non-therapeutic thymectomy is high due to the difficulty in the differential diagnosis of anterior mediastinum lesions. Formerly, it was believed that the thymus gradually degraded and lost function with aging, and the preservation of the thymus was not valued. Recent studies have found that the removal of the thymus at all ages has adverse effects on overall health and leads to a significant increase in the risk of autoimmune diseases, malignancy, and all-cause mortality. Therefore, unnecessary thymectomy should be avoided. This article reviews the influence of thymectomy, including the changes of immunological indexes and clinical prognosis, and further discusses the current situation and avoidance methods of non-therapeutic thymectomy.