P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules
P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules
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DOI：
10.2310/jim.0b013e3181b918fb
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发表时间：
2009-10-01
影响因子：
2.6
通讯作者：
Thorlacius, Henrik
中科院分区：
文献类型：
--
作者：
Asaduzzaman, Muhammad;Mihaescu, Andrada;Thorlacius, Henrik
背景资料：活化的T细胞调节炎症性疾病在肠道，然而，粘附机制CD 8（+）T细胞的募集在colon.Methods：在这里，我们使用了移植物抗宿主病（GvHD）模型来研究CD 8（+）T细胞滚动和粘附在大肠中使用活体荧光显微镜。通过将来自BDF 1，B6，H-2b小鼠的50 x 10（6）同种异体供体脾细胞转移至受体BDF 1，H-2（bxd）小鼠来诱导移植物抗宿主病。8天后，将来自健康和GvHD小鼠的罗丹明标记的CD 8（+）T细胞（4 × 106）注射到健康和GvHD受体小鼠中，并在结肠中研究CD 8（+）T细胞-内皮相互作用。P-选择素和P-选择素糖蛋白配体I的免疫中和作用使炎症结肠小静脉中的CD 8（+）T细胞滚动和粘附减少了71%以上。抑制E-选择素对GvHD诱导的CD 8（+）T细胞-内皮细胞相互作用没有影响。结论：我们得出结论：P-选择素和P-选择素糖蛋白配体I是支持炎症结肠微静脉中CD 8（+）T细胞粘附相互作用的主要分子，可能是保护大肠免受病理性炎症的有用靶点。
Background: Activated T cells regulate inflammatory diseases in the intestinal tract; however, the adhesive mechanisms governing CD8(+) T-cell recruitment in the colon are not known.Methods: Herein, we used a graft-versus-host disease (GvHD) model to study CD8(+) T-cell rolling and adhesion in the large intestine by use of intravital fluorescence microscopy. Graft-versus-host disease was induced by transferring 50 x 10(6) allogeneic donor splenocytes from BDF1, B6, H-2b mice to recipient BDF1, H-2(bxd) mice. After 8 days, rhodamine-labeled CD8(+) T cells (4 x 106) from healthy and GvHD mice were injected into both healthy and GvHD recipient mice, and CD8(+) T-cell-endothelium interactions were studied in the colon.Results: Activated CD8(+) T cells from GvHD mice expressed higher levels of P-selectin ligand and decreased levels of L-selectin. Immunoneutralization of P-selectin and P-selectin glycoprotein ligand I reduced CD8(+) T-cell rolling and adhesion in inflamed colonic venules by more than 71%. Inhibition of E-selectin had no effect on GvHD-induced CD8(+) T-cell-endothelium interactions.Conclusions: We conclude that P-selectin and P-selectin glycoprotein ligand I are dominating molecules in supporting adhesive interactions of CD8(+) T cells in inflamed colonic venules and may be useful targets to protect against pathological inflammation in the large bowel.