血小板对树突状细胞和肿瘤细胞抗原呈递活性的抑制作用

本研究探讨完整的血小板对骨髓来源的树突状细胞（BMDC）和肿瘤细胞的抗原呈递功能的影响。抗原呈递检测体系采用BMDC诱导的混合淋巴细胞反应或肿瘤细胞系EG7（表达卵白蛋白OVA）诱导的OVA特异性T细胞的活化，共培养体系中加入从小鼠外周血分离的血小板至不同浓度，培养一定时间后采用同位素掺入法检测淋巴细胞增殖，采用ELISA检测各种细胞因子的水平，采用流式细胞术检测细胞表面分子情况。结果发现，在反应体系中加入血小板时，淋巴细胞增殖和IFN,,／产生均明显受抑制。血小板还可以阻断细菌脂多糖或含CpG基序的寡核苷酸引起的BMDC表面B7之上调、细胞因子分泌及对同种异基因淋巴细胞的刺激反应。血小板也可抑制BMDC特异性T细胞呈递可溶性或细胞性抗原的能力，表现为淋巴细胞的增殖和细胞因子分泌受到抑制。血小板的这些抑制作用均依赖于加至培养体系中血小扳的浓度。流式细胞术分析表明，血小板结合于BMDC仅轻微增加后者的死亡比例。结论：在某些条件下，血小板可以通过抑制抗原呈递功能而对免疫反应起到负向调控作用，血小板对免疫系统的调节可能比原来预期的更加复杂。

Platelets Inhibit Antigen Presentation by Dendritic Cells and Tumor Cells

This study was aimed to investigate the effects of intact platelets on antigen presentation by either tumor cells or bone-marrow derived dendritic cells (BMDCs).The antigen presentation assay models included BMDC stimulated mixed allogenic lymphocyte reaction and antigen presentation by OVA-harboring EG7 cells to OVA-specific TCR transgenic OT-I T lymphocytes.Fresh platelets prepared from homogenic murine bloods were added to the culture systems to different levels.Lymphocyte proliferation,level of secreted cytokines in the culture and phenotype of BMDCs were measured by isotope incorporation,ELISA and flow cytometry respectively.The results indicated that when platelets at certain concentrations were added in co-culture system containing both OVA-harboring EG7 cells and OVA-specific TCR transgenic OT-I T lymphocytes,both lymphocyte proliferation and IFNγ production were inhibited.The addition of platelets to the BMDC culture followed by LPS or CpG ODN treatment blocked B7-2 upregulation,cytokine production of the BMDCs,and stimulation potency of such BMDCs for allogenic lymphocytes.Furthermore,platelets inhibited the ability of BMDCs to present both soluble and cellular antigens to clonal specific T lymphocytes,which reflected by decreased lymphocyte proliferation and cytokine production.All these platelet-dependent effects were related to the concentrations of platelets in culture.FACS analysis also revealed that platelets bound to BMDCs induced slightly higher cell death rate of BMDCs.It is concluded that under certain conditions,platelets may affect antigen presentation and the overall outcome of immune responses in a negative way,providing new evidence for the hypothesis that platelets play much more complicated roles in the regulation of immune compartments than originally believed.