Gp130分子的活化在树突状细胞分化和成熟中的意义

Significance of gp130 molecule activation in the differentiation and maturation of dendritic cells

目的 :研究激发型抗gp130分子单抗B S12对树突状细胞 (DC)分化成熟和功能的影响。方法 :人外周血单核细胞在GM CSF和IL 4作用下分化为未成熟DC后 ,加入B S12单抗 ,观察它对DC表型、摄取抗原的能力以及DC分泌IL 12、进行混合淋巴细胞反应及趋化T细胞能力的影响 ;同时比较B S12和激发型抗CD4 0单抗 5C11对DC的作用。结果 :激发型抗gp130分子单抗B S12作用于未成熟DC ,可以上调DC上CD1a和共刺激分子CD80、CD86以及成熟DC的标志CD83分子的表达 ,下调CD14的表达 ,降低DC摄取抗原的能力 ,增强DC分泌IL 12、进行混合淋巴细胞反应及趋化T细胞的能力 ,但这些作用都稍弱于 5C11对DC的作用。结论 :未成熟DC上gp130分子的直接活化可以诱导DC的分化和功能成熟。

Objective:To study the effects of agonistic anti gp130 monoclonal antibody B S12 on the differentiation, maturation and function of dendritic cells (DC).Methods:Monocytes isolated from human peripheral blood were cultured with GM CSF plus IL 4, and differentiated into immature DC. The phenotype of DC was analyzed by cytometry after the addition of B S12 antibody to the culture of immature DC. In addition, the abilities for DC to uptake antigen, secrete IL 12, initiate the mixed lymphocyte reaction and chemoattract T cells were tested. The effects of agonistic anti CD40 monoclonal antibody 5C11 on the differentiation, maturation and function of DC were simutaneously compared with those of B S12 antibody.Results:Agonistic anti gp130 monoclonal antibody B S12 had DC to up regulate the expression of CD1a, costimulatory molecules CD80 and CD86 as well as CD83, which is special marker for mature DC, down regulate the expression of CD14. Moreover, B S12 antibody decrease the up take of antigen by DC, enhance the abilities for DC to secrete IL 12, initiate the mixed lymphocyte reaction and chemoattract T cells. The comparison of roles of B S12 and 5C11 antibodies in DC showed that 5C11 was more effective than B S12.Conclusion:The direct stimulation of gp130 on immature DC by B S12 antibody could induce immature DC to differentiate into mature DC.