| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
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
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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
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