Mazerolles F, Barbat C, Meloche S, Gratton S, Soula M, Fagard R, Fischer S, Hivroz C, Bernier J, Sekaly R P
National Institute of Health and Medical Research (INSERM) U 132, Necker Hospital for Sick Children, Paris, France.
J Immunol. 1994 Jun 15;152(12):5670-9.
We examined the role of CD4 and p56lck in the regulation of LFA-1-dependent T cell adhesion to B cells and to fibroblasts expressing ICAM-1 and HLA-DR by using various transfectant constructions. Although CD4 transfection in CD4low HUT78 T cell lines did not significantly modify their maximal binding to B cells and fibroblasts, it made the LFA-1-dependent adhesion sensitive to inhibition by anti-CD4 Ab, HIV-1 (env) gp 160, and a 12-mer peptide encompassing the 35-46 sequence of the beta 1 domain of the MHC class II molecule. CD4low HUT78 T cell adhesion to B cells was stable over 60 min, whereas expression of CD4 led to a transient adhesion. In addition, adhesion of CD4+ T cells to MHC class II- B cells was also stable. The CD4-dependent alteration of adhesion required the association of CD4 with p56lck because expression of mutant forms of CD4 unable to bind p56lck resulted in a lack of CD4-dependent regulation of adhesion. Herbimycin A, an inhibitor of tyrosine kinase activity, reversed the effect of CD4 transfection on adhesion. These results indicate that ligand binding to CD4 delivers a signal-inducing cell dissociation by activating p56lck tyrosine kinase. This regulatory pathway may provide a quick and reliable way for multiple and subsequent Ag-independent adhesion events of CD4+ T cells.
我们通过使用各种转染构建体，研究了CD4和p56lck在调节LFA-1依赖的T细胞与B细胞以及与表达细胞间黏附分子-1（ICAM-1）和人类白细胞抗原-DR（HLA-DR）的成纤维细胞黏附中的作用。尽管在低表达CD4的HUT78 T细胞系中进行CD4转染，并未显著改变其与B细胞和成纤维细胞的最大结合能力，但却使LFA-1依赖的黏附对抗CD4抗体、HIV-1（env）糖蛋白160以及包含MHC II类分子β1结构域35 - 46序列的12肽敏感。低表达CD4的HUT78 T细胞与B细胞的黏附在60分钟内保持稳定，而CD4的表达则导致短暂的黏附。此外，CD4 + T细胞与不表达MHC II类分子的B细胞的黏附也很稳定。CD4依赖的黏附改变需要CD4与p56lck结合，因为无法结合p56lck的CD4突变体形式的表达导致缺乏CD4依赖的黏附调节。酪氨酸激酶活性抑制剂赫司菌素A可逆转CD4转染对黏附的影响。这些结果表明，配体与CD4结合通过激活p56lck酪氨酸激酶传递诱导细胞解离的信号。这种调节途径可能为CD4 + T细胞的多种后续非抗原依赖黏附事件提供一种快速可靠的方式。
