The Function Of NKT Cells In Oral Tolerance Induction By Using Mouse Skin Transplantation Moedl

Object:Here, we investigated the role of NKT in tolerance induction by oral administration in mouse skin grafting. Currently, with the development and efficiency of immunosuppressive drugs, the survival time and the rate of rejection have been decreased significantly. But, the side effects of immunosu-ppressive drugs affected the long term survival of renal graft and the quality of living recipients. Therefore, tolerance induction, rejection reduction and side effects reduction of immunosuppressive drugs, have been the key parts of clinical transplantation. A mount of research have showed that donor antigen oral administration has potential ability to induce tolerance. Furthermore, NKT is kind of subset with special biologic activity, and can play an important role in tolerance induction.Method:Allogeneic mouse tail-back skin graft model has been established successfully. Recipients received donor type splenocyte oral administration, CSA i.p. injection and donor type splenocyte oral administration plus CSA i.p. respectively. Grafts survival was monitored by daily observation. NKT in splenocytes were detected by FACS. The inhibitory effects of NKT isolated from tolerance recipients were detected by adoptive transfer tolerance NKT to naive recipients.Results:(1) The survival time of skin grafts were 12 days, the survival time of oral alone group, CSA alone group and oral+CSA group were 15 days,14 days and 16.5 days, respectively. Compared to naive controls, the survival time of skin grafts in CSA alone group has been prolonged significantly (P<0.0001), the survival time of skin grafts in oral alone group has been increased significantly (P<0.0001), and the effect of tolerance induction better than CSA alone group (P<0.05). The survival time of grafts in oral plus CSA group have been significantly prolonged compared to oral alone group (P<0.01) and CSA alone group (P<0.05), respectively.(2) NKT in splenocytes was detected by FACS. There were no significantly difference of NKT in splenocytes from CSA alone group compared to naive control. But the percentages of NKT in splenocytes from oral alone group increased significantly compared to naive control (P<0.05). The percentages of NKT in splenocytes from oral+CSA group increased significantly compared to oral alone group (P<0.05) and naive control (P<0.001).(3) NKT isolated from tolerance mice induced by oral+CSA has the potential to induce skin grafts tolerance in naive recipients by using adoptive transfer. The skin grafts survival time has been prolonged significantly in adoptive transfer group (P<0.001).Conclusions:Oral administration plus CSA can induce allogeneic skin graft tolerance. NKT increased significantly in tolerance group, and this kind of tolerance of NKT can be transfer to naive recipients by using adoptive transfer.