Studies On The Mechanism Of T Lymphocyte Activity Influenced By Ionizing Radiation

Biological effect of low dose radiation (LDR) has been of great interest inthe field of radiological sciences. LDR enhances the cell-mediated immunity andhumoral-mediated immunity, with the most significant effect at the dose of 0.075Gy radiation. With the development of molecular immunology, the mechanism ofimmuno-enhancment enhanced by LDR has been extensively explored, the chiefunderstanding of which is the initiation of signal transduction, the activation ofTh cells and the inhibition of apoptosis.This thesis systematically studied the time-course and dose-effect changesof PKC theta and LAMP-1 expression in vivo and in vitro after ionizingradiation. The current study supplemented the immune effect of low doseionizing radiation and provided scientific basis for exploring the effect of PKCtheta and LAMP-1 expression changes in immunological signal transduction.With 2.0 Gy X rays, the weight of spleen and thymus in mice and cellcounts decreased gradually in a time-dependent manner, while the apoptosis ofthymocytes increased in a time-dependent manner. The radiation of 0.075 Gy Xrays could improve the quality of spleen and thymus, increase cell accounts andreduce apoptosis to some extent. High dose radiation (HDR) could significantlyinhibit immune system while LDR could stimulate immune system.LAMP-1 participated in the immune signal transduction of ionizingradiation and was found to be associated closely with the immune activity of Tlymphocytes: HDR inhibited the expression of T cells with a decreaseddegradation, however LDR promoted its expression at the early stage;theexpression of LAMP-1 on cell surface was increased when the immunocyteswere activated. Con A promoted the activation of immunocytes with aremarkable increase in expression of LAMP-1 on cell surface. The moreradiation dose was given, the more obvious inhibition of immune system wasobserved, and the expression of LAMP-1 was down regulated. The stimulation ofCon A was able to thoroughly relieve the inhibition of HDR and make theLAMP-1 expression increase with added radiation doses. LAMP-1 played animportant role in immunocyte activation.PKC theta played an important part in signal transduction of T lymphocytesexposed to ionizing radiation. Its kinase acivity was displayed when it transferredfrom cytoplasm to the cell membrane in the immune synapse. Both HDR and LDR couldpromote the expression of PKC theta in cytoplasm and membrane translocation. Themembrane translocation of PKC theta depended on its enhanced expression in cytoplasm.PKC theta served as a downstream signaling molecule for TCR/CD3, with its increasedexpression in the spleen and thymus when T lymphocytes were activated by LDR. Thissuggested that PKC theta was involved in the activation of T lymphocyte exposed toionizing radiation. Its enhanced expression in the thymus may be associated with thematurity of thymocytes. Its participation in immune effect of LDR was regulated by othersignaling molecules in regulatory system of the body. PKC theta showed an enhancedexpression in cytoplasm and an increased membrane translocation, which indicated that itnot only played an important role in T lymphocyte activation but may also be involved inother signal transductions. With a multiple biological activities such as facilitating apoptosis,PKC theta may be an important factor in the influence of ionizing radiation on the bodyimmune functions.