Hauss P, Mazerolles F, Hivroz C, Lecomte O, Barbat C, Fischer A
INSERM U 132, Hôpital Necker Enfants Malades, Paris, France.
Cell Immunol. 1993 Sep;150(2):439-46. doi: 10.1006/cimm.1993.1211.
Antigen-independent adhesion of CD4+ T lymphocytes to Epstein-Barr virus transformed B cells is mainly mediated by LFA-1 (CD11a/CD18) and CD2 molecules. Low-affinity binding of resting T cells can be transiently upregulated by cross-linking of CD3-TCR (T cell receptor) complexes. This inside-out signaling influences integrin (beta 1 and beta 2) adhesion capacity. Studies using the nonspecific inhibitor staurosporine have suggested that this phenomenon is dependent on protein kinase C activation. We found that the upregulation of anti-CD3-activated CD4+ T cell adhesion was inhibited strongly and in a concentration-dependent manner by GF109203X, a compound described as a potent and selective inhibitor of PKC. Comparative studies showed that GF109203X and staurosporine had similar inhibitory effects on the upregulation of activated CD4+ T cell adhesion. However, staurosporine is a nonselective kinase inhibitor. PMA-activated CD4+ T cell adhesion was also inhibited by GF109203X. In contrast, passive enhancement of adhesion by treatment with the CD11a-specific antibody NKI-L16 was unaffected by GF109203X. Taken together, these results show that PKC is involved in upregulating the adhesion of CD4+ T cells to B cells following activation of the former by CD3 cross-linking. PKC-dependent upregulation of CD4+ T cell adhesion to B cells is exclusively LFA-1-dependent, as GF109203X had no additional inhibitory effect on anti-LFA-1 antibody-pretreated T cells activated by the anti-CD3 antibody OKT3 and had no effect on the adhesion of LFA-1(-) CD4+ T cells. Finally, PKC inhibition did not alter CD2-mediated adhesion. This points to a limited participation of CD2 in T-B cell interactions after TCR/CD3 cross-linking.
CD4+ T淋巴细胞与爱泼斯坦-巴尔病毒转化的B细胞的抗原非依赖性黏附主要由淋巴细胞功能相关抗原-1（LFA-1，CD11a/CD18）和CD2分子介导。静息T细胞的低亲和力结合可通过CD3-T细胞受体（TCR）复合物的交联而短暂上调。这种由内向外的信号传导影响整合素（β1和β2）的黏附能力。使用非特异性抑制剂星形孢菌素的研究表明，这种现象依赖于蛋白激酶C的激活。我们发现，GF109203X（一种被描述为蛋白激酶C的强效选择性抑制剂的化合物）以浓度依赖性方式强烈抑制抗CD3激活的CD4+ T细胞黏附的上调。比较研究表明，GF109203X和星形孢菌素对激活的CD4+ T细胞黏附上调具有相似的抑制作用。然而，星形孢菌素是一种非选择性激酶抑制剂。GF109203X也抑制佛波酯激活的CD4+ T细胞黏附。相反，用CD11a特异性抗体NKI-L16处理对黏附的被动增强不受GF109203X影响。综上所述，这些结果表明，蛋白激酶C参与了CD3交联激活后CD4+ T细胞与B细胞黏附的上调。CD4+ T细胞与B细胞黏附的蛋白激酶C依赖性上调完全依赖于LFA-1，因为GF109203X对抗LFA-1抗体预处理后被抗CD3抗体OKT3激活的T细胞没有额外的抑制作用，并且对LFA-1(-) CD4+ T细胞的黏附没有影响。最后，蛋白激酶C抑制并未改变CD2介导的黏附。这表明在TCR/CD3交联后，CD2在T-B细胞相互作用中的参与有限。
