B7/CD28分子激发T细胞抗多发性骨髓瘤细胞的作用

目的探讨Ｂ７／ＣＤ２８分子激发Ｔ淋巴细胞抗多发性骨髓瘤（ＭＭ）作用和提高ＭＭ细胞抗原性的机制。方法采用人Ｂ７１基因对人ＭＭ细胞的转导、ＣＤ２８激发型单克隆抗体（单抗）的激发、同种异体混合淋巴细胞反应（ＭＬＲ）、免疫表型分析和白细胞介素２（ＩＬ２）ＥＬＩＳＡ法定量检测。结果ＸＧ细胞转染Ｂ７１ｃＤＮＡ后，能稳定高表达Ｂ７１，转染Ｂ７１ｃＤＮＡ前后细胞表达ＣＤ１１ａ／ＣＤ１８、ＣＤ４０、ＣＤ５４、ＣＤ５６、ＣＤ５８、Ｂ７２（ＣＤ８６）、ＣＤ４０Ｌ、ＨＬＡⅠ和ＨＬＡⅡ抗原均无明显变化，转染Ｂ７基因后可使肿瘤细胞的抗原性明显增加，在ＭＬＲ中，ＸＧ７１转基因细胞较ＸＧ细胞更能显著介导ＣＤ８＋Ｔ细胞的活化、增殖和ＩＬ２的分泌。ＣＤ２８激发型单抗与Ｂ７１分子相似，能显著介导同种异体Ｔ细胞的混合淋巴细胞反应。结论人ＭＭ细胞不能有效地激发Ｔ细胞抗肿瘤的主要原因之一为其不表达Ｂ７１分子，转染Ｂ７１分子或者加入ＣＤ２８激发型单抗均能有效地提高肿瘤细胞的抗原性和对Ｔ细胞的激发作用，ＣＤ２８激发型单抗临床治疗ＭＭ更具有可行性。

Function of B7/CD28 in antimyeloma immunoreaction through activating T cells

Objective To explore the role of B7/CD28 molecule in priming the antimyeloma effect of T lymphocyte and the mechanism by which CD28 promoted the immunogenicity of myeloma cells. Methods Human B71 gene was transducted into XGs cells. CD28 agonist monoclonal antibody was primed. Primary allogeneic MLR, immunophenotypic analysis and quantitative measurement of IL2 were performed. Results XG cells were successfully transfected with B71 cDNA. The expressions of CD54,CD58, CD11a/CD18, CD40, CD40L, CD56, B72(CD86), HLA and HLA molecules were not affected by the transfection. The transduction of B7 gene dramatically increased the immunogenicity of tumor cells. In allo MLR, the B71 expressing XG cell could more effectively mediate the activation,proliferation and IL2 secretion of alloantigenic CD8 T cells than XG cells did. Like B71 molecules, antiCD28 agonistic McAb could induce the MLR of alloT cell. Conclusion Human multiple myeloma cells failed to induce antitumor immunoreaction because of the weak expression of B7 molecules. The transfection of B71 or CD28 agonist antibody could stimulate and proliferate T lymphocytes and increase the immunogenicity of myeloma cells. CD28 agonist antibody might be promising for clinical application.