Hernández-Caselles T, Martínez-Esparza M, Lazarovits A I, Aparicio P
Department of Biochemistry B and Immunology, Faculty of Medicine, University of Murcia, Spain.
J Immunol. 1996 May 15;156(10):3668-77.
Modulation of VLA integrins was studied in several human T cell clones upon specific and nonspecific cellular activation. Human activated T lymphocytes down-regulated both alpha 4 beta 1 and alpha 4 beta 7 integrins upon specific recognition of alloantigens (cytotoxic T cells) or in the presence of Staphylococcus enterotoxin B (superantigen recognizing noncytotoxic T cells). In contrast, the expression of other membrane integrins, such as VLA-1 and VLA-5 integrins, was not modified. Down-regulation of alpha 4 beta 1 and alpha 4 beta 7 integrins was observed as early as 3 h after stimulation, lasted later than 72 h and was partially inhibited by cytochalasin D. Interestingly, neither target cells nor NK cells modulated CD49d expression after interaction with T cells of K562, respectively, suggesting that CD49d expression was linked to specific T cell activation. The down-regulation of the CD49d chain in T cell clones stimulated with immobilized anti-CD3 mAbs confirmed the role of TCR-mediated activation in CD49d regulation. However, the CD3-independent cellular aggregation induced by soluble anti-CD43 mAb was also able to strongly down-regulate alpha 4 beta 1 and alpha 4 beta 7. The present work shows the first evidence that CD49d subunit-bearing integrin expression is distinctly regulated from other integrins after Ag or superantigen recognition by human activated T cells. CD49d modulation may be relevant for the traffic and tissue localization of locally activated T cells during immune responses.
在几个经特异性和非特异性细胞激活的人T细胞克隆中研究了VLA整合素的调节作用。人活化的T淋巴细胞在特异性识别同种异体抗原（细胞毒性T细胞）时或在存在金黄色葡萄球菌肠毒素B（识别非细胞毒性T细胞的超抗原）的情况下，会下调α4β1和α4β7整合素。相比之下，其他膜整合素如VLA-1和VLA-5整合素的表达未发生改变。早在刺激后3小时就观察到α4β1和α4β7整合素的下调，持续超过72小时，并被细胞松弛素D部分抑制。有趣的是，靶细胞和NK细胞分别与K562的T细胞相互作用后均未调节CD49d的表达，这表明CD49d的表达与特异性T细胞激活有关。用固定化抗CD3单克隆抗体刺激的T细胞克隆中CD49d链的下调证实了TCR介导的激活在CD49d调节中的作用。然而，可溶性抗CD43单克隆抗体诱导的不依赖CD3的细胞聚集也能够强烈下调α4β1和α4β7。本研究首次证明，人活化T细胞在识别抗原或超抗原后，携带CD49d亚基的整合素表达与其他整合素的调节明显不同。CD49d的调节可能与免疫反应期间局部活化T细胞的运输和组织定位有关。
