Expansion of myeloid suppressor cells in SHIP-deficient mice represses allogeneic T cell responses
Expansion of myeloid suppressor cells in SHIP-deficient mice represses allogeneic T cell responses
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DOI：
10.4049/jimmunol.173.12.7324
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发表时间：
2004-12-15
影响因子：
4.4
通讯作者：
Kerr, WG
中科院分区：
文献类型：
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作者：
Ghansah, T;Paraiso, KHT;Kerr, WG
以前，我们证明了SHIP-/-小鼠接受异基因骨髓移植（BMT）没有显着的急性移植物抗宿主病（GvHD）。在这项研究中，我们表明，SHIP-/-脾细胞和淋巴结细胞是不良的刺激同种异体T细胞反应，导致GvHD。有趣的是，SHIP-/-脾细胞引发幼稚T细胞对肽表位的应答，但相反地，引发T细胞对全Ag的应答部分受损。然而，从SHIP-/-脾细胞纯化的树突状细胞（DC）与SHIP+/+ DC一样有效地引发T细胞对同种异体靶标、肽表位和全抗原的应答。这些发现指出了对SHIP-/- DC的外在影响，其损害同种异体T细胞应答的引发。与这种外在效应一致，我们发现SHIP-/-小鼠中髓系抑制细胞的急剧扩增损害了同种异体T细胞的启动。这些发现表明，SHIP表达或其活性可以靶向选择性地损害介导GvHD和移植物排斥的T细胞应答。
Previously we demonstrated that SHIP-/- mice accept allogeneic bone marrow transplants (BMT) without significant acute graft-vs-host disease (GvHD). In this study we show that SHIP-/- splenocytes and lymph node cells are poor stimulators of allogeneic T cell responses that cause GvHD. Intriguingly, SHIP-/- splenocytes prime naive T cell responses to peptide epitopes, but, conversely, are partially impaired for priming T cell responses to whole Ag. However, dendritic cells (DC) purified from SHIP-/- splenocytes prime T cell responses to allogeneic targets, peptide epitopes, and whole Ag as effectively as SHIP+/+ DC. These findings point to an extrinsic effect on SHIP-/- DC that impairs priming of allogeneic T cell responses. Consistent with this extrinsic effect, we found that a dramatic expansion of myeloid suppressor cells in SHIP-/- mice impairs priming of allogeneic T cells. These findings suggest that SHIP expression or its activity could be targeted to selectively compromise T cell responses that mediate GvHD and graft rejection.