Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior.
Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior.
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DOI：
10.1083/jcb.200109098
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发表时间：
2002-04-29
期刊：
影响因子：
--
通讯作者：
Roberts DD
中科院分区：
文献类型：
--
作者：
Li Z;Calzada MJ;Sipes JM;Cashel JA;Krutzsch HC;Annis DS;Mosher DF;Roberts DD
凝血酶敏感蛋白(TSP)-1被报道对T细胞的行为有正向调节和负向调节作用。我们发现，这些相反的反应源于TSP1与两种不同的T细胞受体的相互作用。整合素α4β1识别TSP1NH2末端区域的低密度脂蛋白，是TSP1刺激T细胞黏附、趋化和基质金属蛋白酶基因表达所必需的。T细胞对TSP1的识别依赖于α4β1整合素的激活状态，TSP1可抑制活化的α4β1整合素与其受体受体血管细胞黏附分子1的相互作用。α4β1整合素识别位点在TSP2中是保守的。含有该序列的重组TSP2复制了TSP1的α4β1整合素依赖活性。然而，TSP1中的β1整合素识别位点既不是必要的，也不是充分抑制T细胞增殖和T细胞抗原受体信号的充分必要条件。第二个TSP1受体CD47对TSP1的某些刺激反应不是必需的，但在其T细胞抗原受体拮抗剂和抗增殖活性中发挥重要作用。因此，调节这两种TSP受体的相对表达或功能可能会改变T细胞对TSP的反应方向或幅度。
Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both positively and negatively. We found that these opposing responses arise from interactions of TSP1 with two different T cell receptors. The integrin α4β1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and was required for stimulation of T cell adhesion, chemotaxis, and matrix metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells depended on the activation state of α4β1 integrin, and TSP1 inhibited interaction of activated α4β1 integrin on T cells with its counter receptor vascular cell adhesion molecule-1. The α4β1 integrin recognition site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence replicated the α4β1 integrin–dependent activities of TSP1. The β1 integrin recognition sites in TSP1, however, were neither necessary nor sufficient for inhibition of T cell proliferation and T cell antigen receptor signaling by TSP1. A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSP1 but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities. Modulating the relative expression or function of these two TSP receptors could therefore alter the direction or magnitude of T cell responses to TSPs.
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