Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo
Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo
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DOI：
10.1046/j.1365-2567.1999.00794.x
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发表时间：
1999-07-01
期刊：
影响因子：
6.4
通讯作者：
Merino, J
中科院分区：
文献类型：
--
作者：
López-Hoyos, M;Revilla, C;Merino, J
粘附分子在参与特异性免疫应答的细胞相互作用中至关重要。它们用于归巢、细胞迁移、细胞-细胞接触，并且在某些情况下用于递送共刺激信号。由于宿主抗移植物（HVC）反应代表了一种特殊形式的T-B细胞相互作用，我们已经探索了淋巴细胞功能相关抗原-1/细胞内粘附分子-1的抑制是否LFA-1/ICAM-1相互作用和通过极晚期活化抗原-4（VLA-4）的信号传导对出生时注射LFA-1/ICAM-1的BALB/c小鼠中狼疮样疾病的发展具有任何影响。（BALB/c x C57 BL/6）F-I脾细胞。与对供体同种异体移植物耐受性的发展密切相关，这些小鼠表现出同种异体反应性宿主CD 4（+）T细胞对F-1供体B细胞的多克隆激活，表现为自身抗体（自身抗体）的产生和轻度肾小球肾炎的发展。已调整所用单克隆抗体（mAb）的剂量，以完全阻断外周淋巴细胞表面上的分子，而不干扰新生儿耐受性的诱导。注射饱和剂量（100 μ g/2天）的抗-LFA-1 α或抗-ICAM-1单克隆抗体，但不注射抗-VLA-4 α或抗-LFA-1 β单克隆抗体，阻断抗-ssDNA自身抗体的产生和该HVG疾病（HVGD）特征性的血小板减少。然而，抗VLA-4 α治疗仅能够延迟自身抗体的产生和抗LFA-1 β治疗，而不能改变HVGD的演变。这些结果表明，在HVGD中宿主2型T辅助细胞和供体B细胞之间的同种异体相互作用期间发生的多克隆B细胞活化中，LFA-1/ICAM-1相互作用相关，而VLA-4介导的信号无关。
Adhesion molecules are critical in the cellular interactions involved in specific immune responses. They are used for homing, cell migration, cell-cell contact and, in some cases,for the delivery of costimulatory signals. Since the host-versus-graft (HVC) reaction represents a particular form of T-B-cell interaction, we have explored whether the inhibition of lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) interactions and the signalling through very late activation antigen-4 (VLA-4) have any effect on the development of a lupuslike disease in BALB/c mice injected at birth with (BALB/c x C57BL/6)F-1 spleen cells. In close association with the development of tolerance to donor allografts, these mice show a polyclonal activation of F-1 donor B cells by alloreactive host CD4(+) T cells, manifested by the production of autoantibodies (autoAbs) and the development of a mild glomerulonephritis. The dose of the monoclonal antibody (mAb) employed has been adjusted to block completely the molecule on the surface of peripheral lymphocytes without interfering with the induction of neonatal tolerance. Injection of satarating doses (100 mu g/2 days) of either anti-LFA-1 alpha or anti-ICAM-1 mAbs, but not anti-VLA-4 alpha or anti-LFA-1 beta mAbs, blocks the production of anti-ssDNA autoabs and the thrombocytapenia characteristic of this HVG disease (HVGD). However, anti-VLA-4 alpha treatment is only able to delay the production of autoAbs and the anti-LFA-1 beta treatment, not to modify the evolution of the HVGD. These results point to the relevance of LFA-1/ICAM-1 interactions, but not of the VLA-4-mediated signal, in the polyclonal B-cell activation occurring during the allogeneic interactions between host T helper type 2 cells and donor B cells in HVGD.