| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 96 === Coinhibitory signal mediated via programmed death 1 (PD-1) plays a critical role in down-regulating immune responses and maintaining peripheral tolerance. Since PD-1 provides the negative signaling upon interaction with its ligands, PD-L1 or PD-L2, we generated the transgenic NOD mice overexpressing PD-L1 or PD-L2 in pancreatic cells to see whether the “additional” inhibitory signal provided by transgenic PD-L1 or PD-L2 can protect mice from autoimmune diabetes. Our results indicated that both transgenic lines displayed an islet-specific expression of PD-L1 or PD-L2 transgene, respectively. The spontaneous diabetic incidences were markedly decreased both in PD-L1 and PD-L2 transgenic mice, although the PD-L1 transgene provided better protection than did PD-L2. To investigate whether the protective mechanism works through down-regulation of diabetogenic T cells, we performed an adoptive transfer experiment in the NOD/SCID system. NOD/SCID mice receiving lymphocytes from PD-L1 or PD-L2 transgenic mice became diabetic with slower kinetics compared to mice receiving lymphocytes from their non-transgenic controls. Moreover, lymphocytes collected from NOD/SCID recipients that previous receiving lymphocytes from PD-L1 or PD-L2 transgenic mice revealed less proliferative potential than lymphocytes obtained from recipients that previous receiving lymphocytes from control mice. Islets in diabetic recipients that received lymphocytes from PD-L1 transgenic mice survived moderately longer than control islets. We illustrate the modulatory roles of PD-L1 and PD-L2 in down-regulating diabetogenic T cells in NOD mice. In summary, our results demonstrate that enhancing PD-1 signaling by the presence of either transgenic PD-1 ligands provides beneficial immune modulation in autoimmune diabetes.
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