LFA-1/ICAM-1在ConA诱导的小鼠胸腺细胞活化中的作用

用抗LFA-1/ICAM-1粘附分子单克隆抗体和ConA联合刺激小鼠胸腺细胞,初步研究了该膜分子在经TCR/CD3介导的胸腺细胞活化信号传导以及胸腺细胞亚群选择中的作用。在ConA刺激系统中,抗ALFA-1/ICAM-1单抗均能抑制胸腺细胞的增殖应答,且以抗LFA-1单抗的作用更为显著;而在PMA加钙离子载体A23187刺激体系中,抗LFA-1单抗却表现出明显的促活化效应。当加入IL-2 时,抗LFA——1/ICAM-1单抗便不能抑制ConA刺激的胸腺细胞活化。此外,抗体对已活化的胸腺母细胞增殖也无影响。FACS分析的结果还显示,抗LFA-1单抗可明显降低CD4~-CD8~ 胸腺细胞亚群的比例,而抗ICAM-1单抗对此无影响。表明胸腺细胞表面粘附分子LFA-1具有直接参与TCR/CD3途径介导的跨膜信号传导的功能,并对CD4~-CD8~ 胸腺细胞亚群的功能分化与成熟可能起重要作用。

ROLE OF LFA-1/ICAM-1 IN THE ACTIVATION OF MURINE THYMOCYTES STIMULATED BY CON A

The biological significance of the signals triggered by the interaction of cell surface expressed LFA-l and ICAM-1 has been investigated in Con A stimulated mu-rine thymocytes. Addition of anti-LFA-1 or/and anti-ICAM-1 McAb to the thymo-cyte culture in the presence of Con A, the cell proliferation was profoundly inhibited. Such inhibitory effect was more significant by the addition of anti-LFA-1 than by the addition of anti-ICAM-l McAb. FACS analysis revealed that the proliferation of CD8 T cells was more sensitive to the inhibitory effect of anti-LFA-l McAb than did the proliferation of CD4 T cells. The anti-LFA-1 McAb imposed inhibitory effect, however, could be reversed by the supplementation of IL-2 in the initiation of the culture. The proliferation of cultured Con A activated T blast cells could no longer be inhibited by the addition of anti-LFA-l McAb. Furthermore, neither anti-LFA-l nor anti-ICAM-1 McAb could block PMA A23187 induced thymocyte proliferation. The results imply that the ligand-receptor pair of LFA-l-ICAM-1 molecules also takes part in the early events of Con A activated signal transduction pathway which leads to the proliferation of thymocytes.