LPAM(α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease
LPAM(α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease
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DOI：
10.1182/blood-2003-03-0957
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发表时间：
2004-02-15
期刊：
影响因子：
20.3
通讯作者：
van den Brink, MRM
中科院分区：
文献类型：
--
作者：
Petrovic, A;Alpdogan, O;van den Brink, MRM
淋巴细胞派尔斑粘附分子（LPAM）或α（4）β（7）整联蛋白在淋巴细胞上表达，并通过与粘膜地址素细胞粘附分子（MAdCAM）结合（MAdCAM存在于粘膜淋巴器官的高内皮微静脉上），负责T细胞归巢至肠相关淋巴组织。我们在小鼠异基因骨髓移植（BMT）模型中发现，与α（4）β（7）（+）供体T细胞的受体相比，α（4）β（7）（-）供体T细胞的受体的移植物抗宿主病（GVHD）发病率和死亡率显著降低。肠和肠系膜淋巴结中淋巴细胞的动态移植后分析表明，与α 4 β 7 + T细胞受体相比，α 4 β 7 + T细胞受体中α 4 β 7 + T细胞数量较低。对GVHD靶器官的组织学分析显示，α 4 β 7-T细胞受体发生肠和肝脏GVHD较少，而α 4 β 7-T细胞受体和α 4 β 7 + T细胞受体之间的皮肤和胸腺GVHD没有差异。最后，我们发现α（4）β（7）（-）供体T细胞的体内GVT活性得以保留。我们的结论是，α（4）β（7）整合素是重要的同种异体反应性供体T细胞进入肠道和肠道GVHD的发展和整体GVHD的发病率和死亡率的入侵。
Lymphocyte Peyer patch adhesion molecule (LPAM) or alpha(4)beta(7) integrin is expressed on lymphocytes and is responsible for T-cell homing into gut-associated lymphoid tissues through its binding to mucosal addressin cell adhesion molecule (MAdCAM), which is present on high endothelial venules of mucosal lymphoid organs. We found in murine allogeneic bone marrow transplantation (BMT) models that recipients of alpha(4)beta(7)(-) donor T cells had significantly less graft-versus-host disease (GVHD) morbidity and mortality compared with recipients of alpha(4)beta(7)(+) donor T cells. A kinetic posttransplantation analysis of lymphocytes in the intestines and mesenteric lymph nodes demonstrated a delayed invasion of lower numbers of alpha(4)beta(7)(+) T cells in recipients of alpha(4)beta(7)(-) T cells compared with recipients of alpha(4)beta(7)(+) T cells. Histopathologic analysis of GVHD target organs revealed that recipients of alpha(4)beta(7)(-) T cells developed less GVHD of the intestines and liver, whereas there was no difference in cutaneous and thymic GVHD between recipients of alpha(4)beta(7)(-) or alpha(4)beta(7)(+) T cells. Finally, we found that in vivo GVT activity of alpha(4)beta(7)(-) donor T cells was preserved. We conclude that the alpha(4)beta(7) integrin is important for the invasion of alloreactive donor T cells into the gut and the subsequent development of intestinal GVHD and overall GVHD morbidity and mortality.