Regulatory mechanisms of graft rejection and graft recurrence of IDDM by NKT cells in pancreaticoduodenal transplantation.

在Wistar-Furth(WF；RT1^u RT6.2)到自发性糖尿病易感(DP；RT1^u，RT6.1基因携带者)-BB全胰十二指肠移植(PDTX)模型中，供者来源的RT6^+T细胞(Tx后120天)出现大嵌合体(34.3%)。鉴于NKR-P1+TCRαβ^+(NKT)细胞参与免疫调节功能，如控制自身免疫性疾病的发生，本研究旨在阐明NKT细胞与IDDM复发的关系。在检测细胞免疫反应的同时，用流式细胞仪分析未复发的DP大鼠的脾和肝细胞，用ELISA法测定血清细胞因子(IL-4和干扰素-γ)水平，并与复发的PDTX-DP受体(无单抗)、复发的…进行比较RNT单独移植的DP(PATx-DP+mAbbs)、DP和WF大鼠较多。在接受胰腺移植的DP受者的脾细胞中，45.6(35-55)%的T细胞是供体来源的RT6.2^+T细胞。三色流式细胞仪分析显示，NKT细胞明显增殖，占脾T细胞总数的20~30%，并伴有RT6~+NKT细胞数量(绝对数)的增加，而RT6~+NKT细胞在各组间无明显差异。供者来源的RT6.2^+NKT细胞在未复发的DP受体的肝脏中也可观察到增殖。另一方面，在复发DP受者的脾细胞中未检测到大嵌合(和NKT细胞的增殖)。在相同的mAbs治疗下，糖尿病抵抗(DR；RT1^u，RT6.1)-BB大鼠的移植排斥反应(包括IDDM复发)也能被抑制，其机制与移植肾中rt6+T细胞的再生机制类似。提示供者来源的rt6+NKT细胞可能与抑制IDDM复发和移植物排斥反应有关。较少

We previously domonstrated that IDDM graft recurrence could be prevented with the administration of anti-ICAM-1/LFA-1 mAbs, resulting in the appearance of macrochimerism (34.3%) of donor-derived RT6^+ T cells (120 days postTx) in a Wistar-Furth (WF ; RT1^u RT6.2) to spontaneously diabetes prone (DP ; RT1^u, RT6.1 gene carrier)-BB whole pancreaticoduodenal transplantation (PDTx) model. As NKR-P1^+TCRαβ^+ (NKT) cells have recently been demonstrated to be involved in immunoregulatory functions such as the control of occurrence of autoimmune diseases, the purpose of this study was to clarify the relationship between NKT cells and IDDM recurrence in this model. In addition to the examination of cellular immune responses, the cells of the spleen and liver of these nonrecurrent DP rats were analyzed in terms of NKT cells by flow cytometric analysis, and serum cytokine levels (IL-4 ＆ IFN-γ were determined by ELISA, as comparing with those of recurrent PDTx-DP recipients (without mAbs), recurre … More rnt pancreas-alone transplanted DP (PATx-DP with mAbs), DP, and WF rats. In the spleen cells of the DP recipients that had accepted pancreatic grafts, 45.6 (35-55) % of the total splenic T cells were donor-derived RT6.2^+ T cells as early as 60 days postgrafting. A three color flow cytometric analysis showed that NKT cells had proliferated markedly, with the proportion of 20-30% in the total splenic T cells, accompanied by the increased population (absolute number) of RT6^+ NKT cells, though those of RT6^- NKT cells were similar in each group. The proliferation of donor-derived RT6.2^+ NKT cells wsa also observed in the liver of the non-recurrent DP recipients. On the other hand, macrochimerism (and the proliferation of NKT cells) was not detected in the spleen cells of the recurrent DP recipients. By ELISA, serum IFN-γ was not detected (<13 pg/ml) in all, but IL-4 was detected as 158.8 pg/ml in the non-recurrent DP recipients.With the same mAbs treatment, graft rejection (including IDDM recurrence) of Diabetic resistant (DR ; RT1^u, RT6.1)-BB rats could be also inhibited in the DP recipients by the similar mechanism of NKT cells in the reappearance of RT6+T cells.Our data indicate that donor-derived RT6^+ NKT cells which originated from the lymphoid tissues of the donor pancreaticoduodenal grafts might be related to the inhibition of IDDM recurrence and graft rejection with a Th2 deviation. Less