The Role Of Natural Killerlymphocytes And Natural Killer T Cells In Different Immune State In Kidney Transplant Patients

One of the 20th century's most brilliant achievements in the medical field is to make the organ transplant as treatment for end-stage disease, With rapid development of the field in transplantation, Transplantation immunity has become a hot area of research. How to adjust immunosuppression programs and the drug dose after transplantation to the immune status in the balance between rejection and infection, how to reduce or avoid renal toxicity of the immunosuppressive drugs, especially calcineurin inhibitor is a problem to each a kidney transplant clinicians. Current mechanism of transplantation immunology focused on the humoral and cellular immunity, with the knowledge of the mechanisms of transplantation immunity gradually deepened, a variety of strategies to monitor the state of transplantation immunity has been used in experimental and clinical. But the cellular and humoral immunity is clearly still in the starting line only, and now no one clinical test of renal transplant recipients is universal acceptance to evaluate immune status.The commonly used indicators are:monitoring of serum creatinine and blood urea nitrogen, application of color Doppler to understand the shape of graft,renal artery resistance index,renal blood flow, application of CT to understand renal sinus and renal morphology, using dynamic magnetic resonance imaging to understand corticomedullary time-signal intensity curve (STC) peak, application of renal puncture biopsy, CSA and FK506 blood concentration testing. With the development of experimental and clinical research, more and more immunologic content is concerned about。T cells were the first entering the field of researchers, CD4/CD8 cell have become an indicator of immune in transplant patients, Treg, regulatory dendritic cells and natural killer cells was also in the experimental stage of exploration. Humoral rejection such as HLAⅠclasses,ⅡClass antibodies and MICA antibody monitoring, and C4d, blood CD 15s antigen, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-αand other Cytokines, urinary protein genomics are also in exploration. Although these research have made some progress, but still no one of them can be thought a very reliable marker to evaluate the immune status for clinical transplant recipients. The clinical signs,symptoms and a variety of methods are combined and applied in transplant recipients, hoping to accurately determine the deficiency and excessive of immune status in the recipients, and hoping to a reasonable application of immunosuppressive drugs.The first part explores the expression of NK and NKT cells in the kidney transplant patients after cytomegalovirus infection with adversing tacrolimus-based immunosuppressive therapy to cyclosporin.Objective The incidence of rejection in tacrolimus-based immunosuppressive therapy group was significantly lower than that in cyclosporine-based immunosuppressive therapy group, and with few side effects. Therefore, tacrolimus treatment is widely used in more and more transplant center. With the increase of renal transplantation, complicated infections such as cytomegalovirus (CMV) infection in transplant patients become common. When patients with tacrolimus-based immunosuppressive therapy appear active or latent CMV infection, tacrolimus always is reduced or unused, or steroids is only used, Rejection may happen, resulting in loss of graft function. Safety and immune status will be evaluated converting tacrolimus to cyclosporine-based immunosuppressive in these patients with CMV infection.Method Patients after renal transplantation more than 3 months were treated with triple immunosuppressive treatment of tacrolimus (0.1-0.15mg/kg/d)+ mycophenolate mofetil MMF (750mg q12h)+steroids (5mg/d), and were infected with active or latent CMV infection,54 patients were randomLy divided into 2 groups according to 1:1, in addition to supported for anti-virus and symptomatic treatment, the immunosuppressive treatment were adjusted as follows:group A:CsA adversion group, cyclosporine A (3-5mg/kg/d)+mycophenolate mofetil MMF (0-250mg q12h)+oral or intravenous methylprednisolone; Patients were treatment with fast conversion method, immediately conversion tacrolimus to cyclosporine. concentration of cyclosporine was monitored 5-7 days after taking CsA, target concentration was 100-150ng/L.group B:tacrolimus reduction group,tacrolimus (0-0.05mg/kg/d)+MMF (0-250mg ql2h)+oral or intravenous methylprednisolone. If patients in these treatments persist fever over 38 degrees more than 3 days, or infect increase with the clinical and laboratory tests, then remove the immunosuppressive drugs of CNI and MMF.Indicators were observated:at the beginning of the 4,8 weeks after treatment, all patients were evaluated.monitoring of serum creatinine, creatinine clearance rate, the incidence of acute rejection, mortality and graft loss rate, pulmonary infection, monitoring blood CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+ NK, CD3+CD16+CD56+ NKT cells and CMV DNA quantitativeResults Two groups of patients were no significant differences in graft survival and mortality rate, FK506 decrese group and the CSA adverse group of 1-8 weeks in the treatment of blood concentrations were maintained at (3.1±1.2)μg/L and 124±42ug/L, These showed that the average serum creatinine in CsA group,recovery earlier than in FK506 group. But it was not significantly different between two groups at week 8. CD4/CD8 and CD3-CD16 CD56 in the CsA group the first 2 weeks up to 4 weeks and 8 weeks to reach a plateau curve, CD4/CD8 and CD3-CD16 CD56 in the FK506 group increased when the first 2 weeks, to 8 weeks to the peak value, which suggested that the patient recovered rapidly from immunosuppression state when half dose of cyclosporine was applied. CD3 CD16 CD56 cells and the group at all time points, there are also significant differences like CD3-CD16+CD56+ cells. At weeks 2 Cytomegalovirus quantitatively in CsA group was significantly lower than in FK506 group, to weeks 8 CMV quantitative in two groups were reduced to less than103 copy per mL.Conclusion Patients with CMV infection after renal transplantation were treated with anti-virus and other symptomatic treatment, application of tacrolimus reduction and cyclosporine conversion programs have good patient and graft survival. Use of tacrolimus in renal transplant recipients in the event of CMV infection, converted into CsA and mycophenolate mofetil immunosuppressive regimen, the cellular immune recoved earlier, Cytomegalovirus was significantly reduced earlier in weeks 2, thus reduced hospital stay and save hospital costs. CD3-CD16+CD56+Nkcells and CD3+CD16+CD56+NKT cells in the transplanted kidney plays an important role in immune. Its expression can predict the extent of infection before and after adjustment immunosuppressive drugs. Its expression can provide a clue for Immune status in prevention and treatment of cytomegalovirus infection at the same time, assess the possibility of CMV virus combination with rejecti o.The second part explores CD3+CD16+CD56+natural killer T (NKT) cells in the peripheral blood in graft rejection and in different blood concentrations.Objective NK and NKT cells present in renal transplantation and its mechanism is still unkwown. This article discusses CD3+CD16+CD56+ natural killer T (NKT) cells in the peripheral blood between different immuno state and different blood concentrations. The purpose of this study is to explore the peripheral blood NK and NKT cells can reflect the immune status as an indicator, combination with clinical expression. According to NKT cells immunosuppressive drugs can be adjusted.Methods 92 patients after renal transplantation were divided into three groups according to rejection and the concentration of calcineurin inhibitor: patients without rejection and within normal concentration range (group A), patients without rejection and within lower concentration range (group B), patients with rejection (group C),10 healthy individuals were selected as controls. The proportion of CD3+,CD3+CD4+,CD3+CD8+,CD3-CD16+CD56+ NK CD3+CD16+CD56+ NKT cells and panel reactive antibody(PRA) were analyzed using flow cytometry.Results The proportion of NKT cells in the patients of group A, group B, group C, and group D were (4.29±3.57)%,(4.31±3.08)%,(1.23±1.06)%,(3.98±2.26)%,respectively. The proportion of NKT,NK cells,CD4+/CD8+,PRA in group A and B did not change significantly compared to those in group D.The proportion of CD3+CD16+CD56+ NKT cells in the peripheral blood of patients was lower in group C compared with that in group D, Significant increase in NKT,NK,CD4+/CD8+,PRA were observed in group CConclusions Monitoring of the expression of CD3+CD16+CD56+ NKT cells in peripheral lymphocytes after renal transplantation may contribute to immune Status. Lower proportion of the CD3+CD16+CD56+ NKT cells indicate rejection. The expression of NKT cells were not affected by lower concentration in patients without rejection. Natural killer T (NKT) cells play an important role in renal transplantation. Analysis of NKT cells can identify patients at risk of graft rejection, and can allow minimization of calcineurin inhibitor and avoidance of its side effects.NK and NKT cells in kidney transplantation and their mechanism are still unkown,To some extent,project design of this study provides a new way of thinking for predicting the clinical immune status of patients.when NK cells, NKT cell level, T lymphocyte subsets tests showed high immune status in the transplant recipients, suggesting that there may exist high risk of rejection; When They showed low immune status, suggesting that the high risk of infection, The program and dose of immunosuppressive drugs should be adjusted. Since human peripheral blood lymphocyte subsets, NK cells, NKT cells are individual differences in a larger proportion, systematic observation of each subsets of peripheral blood CD variation should be does. Postoperative infection in renal transplant recipients for prevention, diagnosis and treatment will be of great help. Current study shows that NK and NKT cells play a important role when used in prevention and detection of transplant rejection and infection,used in monitoring and adjustment the immunization state. This type of cell in the role of transplantation immunity opens a new window, provides a new way of thinking for predicting the clinical status of the patient's immune.