Explore The Immune Status In Vivo During The Early Stage With T Subsets And Cytokines After Renal Transplantation

Background: The immune status in vivo during its early stage is attracting attention in the clinic because recipients with rejection, infection, delayed allograft function and acute toxicity have poor allograft survival for short and long periods after renal transplantation. These clinical episodes reflect that there are two different immune status in vivo during the early stage, as the intervention of immunosuppressive drugs. The two different immune status consist of over-immunosuppresive and under-immunosuppresive. The former leads to various infection and latter represents an acute rejection after renal transplantation. The early diagnosis and prompt anti-rejection therapy for acute allograft rejection can help to reduce these clinical episodes and improve renal allograft survival, but there are absent effective noninvasive tools for early diagnosis in the clinic. Testing T cell subsets and cytokines with biochemical and cellular immunological skills, provide us with ideal tools that can be used to diagnose acute rejection in the early stage and explore the immune status in vivo in the clinic. Although T cell subsets and cytokines have proved sensitive and specific in animal models, there is no consistence in the clinic for its testing value.Objective: To study the variation of T cell subsets and cytokine in the different immune status in vivo during early stages after renal transplantation in the basic and clinical research, and to explore therelationship between the change of testing markers and clinical episodes, the value of the change for early diagnose, and the clinical factors of the change.Methods: The research can be divided into two parts, including of basic and clinical. The basic study was composed of building renal allograft models and monitoring cytokine during acute rejection in rats. The clinical study deals with the effect of renal transplantation between different nationalities in acute rejection, and the study of the immune status with T cell subsets and cytokines during the early stage. The study was performed with the paired groups of both basic and clinical monitoring of T cell subsets and cytokines in vivo with ELISA,and flow-cytometry. T cell subsets included CD3+,CD4+,CD8+and CD3+CD25+T cells and cytokines were IL-2,IFN-y,IL-4,IL-10 and SIL-2R.Results: First we successfully built the model of renal allograft in rats.The average total time of operation was 108+15minutes and a successful rate of 83.3% was achieved in the manipulation. Secondly, the levels of IL-2? IFN-y in rats significantly increased in acute allograft rejection in the early stage, and decreased slowly afterwards. There was no significant increase of IL-4 occurred in contrast with the control (P > 0. 05) and no significant relation between the seriousness of pathological lesion and the high levels of IL-2 and IFN-y. Thirdly, the 1 year survival and rate of acute rejection for the minority receiving Han donors kidney are 89.1% and 25% respectively, higher than Han patients 81.3% and 25.6%, but not significant. Finally, in clinical prospective and paired group trials, the levels of cytokines were not different between normal control and both acute and non-acute rejection groups before renal transplantation. After allograft transplantation, all cytokines significantly increased and were higher in both acute and non-acute renal rejection than in normal control at the first week and from the second week they aregradually close to normal levels.The levels of IL-2 and IFN-y were higher in the acute renal rejection than in non-acute rejection during the first week (during rejection ) and from the second week (after anti-rejection therapy) they gradually returned to the same levels of the non-acute rejection group. There was no significant differences in the levels of IL-4 and IL-10 between acute and non-acute rejection groups during the whole time. The number of CD3+and CD4+T cells were significantly lower in the acute than in the non-acute rejection (P<0.05) during the first and second week and at the same time the levels of sIL-2R were significantly higher in both acute and non-acute rejection than in the normal control, but there was no difference between the acute and non-acute rejection. From the third week the variation of T cell subsets was close to same levels in both groups.Conclosion: We built the first renal allograft model in rats in Xinjiang, and established essential skills and conditions for experiments in rats. Then the results indicated that the levels of Thl cytokines (IL-2 and IFN-y) significantly increased and Th2 cytokine (11-4) had no change in vivo during acute allograft rejection in rats. This proved that ELISA can be used to test the serum levels of cytokines. The serum IL-2, IFN-y might reveal early diagnosis of acute allograft rejection. In clinical investigations, the survivel of minority receiving Han's kidneys at 1 year was similar Han that we made although the acute rejection rate was little higher than Han. The conclusions about T subsets and cytokines in the clinical trials as follows: ? the results indicated that a single cytokine or T cell subset had no clinical diagnosis value, and be useful with the combination of different cytokines and T subsets for early acute rejection.? As similar to the case in rats ,we suggested that the levels of L-2, IFN-y obviously increased and CD3+ CD25+ T cells relatively active in acute renal rejection and also showed that therapy with immunosuppressive drugs is effective when the levels of L-2, IFN-ygradually returned to normal and CD3+CD25+T was a little active.? we definitely suggested that the first three months should be adapted as the early stage of renal transplantation for monitoring the immune status and emphasized that the first two weeks was important for monitoring cytokines and the first month for T cell subsets.? Lastly we proposed that it should be adopted for the paired groups, to kinetically monitor,with combined cytokines with T cell subsets when a clinical trial for investigating the immune status in vivo is performed during early stage after renal transplantation.