中文摘要：

最近， apoptosis 被认为是为 allograft 幸存的一个重要管理者。serine/threonine kinase Pim2 在许多 apoptotic 小径被含有。在以前的研究，我们发现 pim2 高度在一个 allograft 模型在 CD4 ⁺ T 房间被表示。这里，我们进一步在 allograft 幸存和与 apoptosis 联系的内在的机制上调查了 Pim2 的效果。当尖锐 allorejection 发生了时，结果证明 pim2 是在接枝和怒气的 overexpressed，特别地在怒气 CD4 ⁺ T 房间，并且与拒绝的程度断然相关。在从天真的 BALB/c 的怒气的 T 房间，老鼠与 5 对待 µ；为 24h，增加的 apoptosis 率和 phosphorylation 的 M 4a (Pim2 的一个特定的禁止者) 坏被减少。而且， CD4 ⁺ T 房间的采纳转移在 vitro 与 4a 对待到严重联合免疫不全(SCID ) 老鼠有效地延长了的 allografted 从 19.5 ± 的 allograft 幸存； 1.7 天到 31 ±； 2.3 天。而且，结果证明 CD4 ⁺ CD25 ⁻ 受动器 T 房间子集作为与 CD4 ⁺ CD25 ⁺ 规章的 T (Treg ) 房间子集。导致 Alloantigen 的 CD4 ⁺ CD25 ⁺ T 房间与受动器 CD4 ⁺ 与 4a 对待的 CD25 ⁻ T 房间。一起，这些数据表明 Pim2 首先由 modulating 便于 allograft 拒绝受动器 T 房间的 apoptosis 和 Treg 房间的函数。这些数据建议那 Pim2 可以是一个重要目标为在 vivo 反拒绝治疗并且为 CD4 ⁺ CD25 ⁺ T 房间。

英文摘要：

Recently, apoptosis has been considered to be an important regulator for allograft survival. The serine/threonine kinase Pim2 has been implicated in many apoptotic pathways. In a previous study, we found that pim2was highly expressed in CD4＋ T cells in an allograft model. Here, we further investigated the effects of Pim2 on allograft survival and the underlying mechanisms associated with apoptosis. The results showed that pim2 was overexpressed in grafts and spleens, particularly in spleen CD4＋ T cells when acute allorejection occurred, and correlated positively with the extent of rejection. In T cells from the spleens of naive BALB/c mice treated with 5 pM 4a （a specific inhibitor of Pim2） for 24 h, the apoptosis rate increased and the phosphorylation of BAD was decreased. Furthermore, adoptive transfer of CD4＋ T cells treated with 4a in vitroto allografted severe combined immunodeficiency （SCID） mice effectively prolonged allograft survival from 19.5± 1.7 days to 31 ±2.3 days. Moreover, the results demonstrated that the CD4＋CD25- effector T-cell subset was the predominate expresser of the pim2 gene as compared with the CD4＋CD25＋ regulatory T （Treg） cell subset. AIIoantigen-induced CD4＋CD25＋ T cells displayed less Foxp3 expression and a low suppression of apoptosis compared with effector CD4＋CD25- T cells treated with 4a. Collectively, these data revealed that Pim2 facilitated allograft rejection primarily by modulating the apoptosis of effector T cells and the function of Treg cells. These data suggested that Pim2 may be an important target for in vivoanti-rejection therapies and for the ex vivoexpansion of CD4＋CD25＋ T cells.