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DC—SIGN在树突状细胞传播HIV-1中作用的实验研究

The role of DC-SIGN in HIV-1 transmission through dendritic cells
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摘要 目的探讨DC-SIGN在树突状细胞(DC)传播HIV-1中的作用。方法用M嗜性或T嗜性HIV-1原代分离株分别刺激未成熟DC(immature DC,iDC))和成熟DC(mature DC,mDC),数量与DC相同的CD4^+ T细胞作为对照组,与活化的CD4^+ T细胞共培养,用ELISA方法定量检测第4、7、10、14天共培养上清中p24抗原,观察DC在传播HIV-1的作用。预先加入抗DC-SIGN McAb和/或抗ICAM-3 McAb,观察抗DC-SIGN McAb和抗ICAM-3 McAb对DC传播HIV-1作用的影响。结果用M嗜性HIV-1刺激的iDC以及用M和T嗜性HIV-1刺激的mDC的共培养上清中p24含量均随培养时间延长逐渐增加,显著高于对照组(P=0.001)。加入抗DC-SIGN McAb后,共培养上清p24抗原明显降低;加入抗ICAM-3 McAb后上清中p24抗原并不减少。用T嗜性HIV-1刺激的iDC共培养上清中p24含量不随培养时间延长逐渐增加,与对照组相比差异无统计学意义。结论iDC具有传播M嗜性HIV-1的作用,但不具有传播T嗜性HIV-1的作用;mDC既能将M嗜性也能将T嗜性HIV-1传播给CD4^+ T细胞。抗DC-SIGN McAb能够抑制DC传播HIV-1的作用,提示DC-SIGN在DC向T细胞播散HIV-1过程中可能发挥重要作用。 Objective To identify the role of DC-SIGN in HIV-1 transmission by peripheral dendritic cells （DC）. Methods Immature DC（iDC） and mature DC（mDC） stimulated with M- or T-tropic HIV-1 primary isolates were eocultured with activated CD4^＋T cells. The level of HIV-1 p24 antigen in coculture supernatant was detected by quantitative ELISA method at day 4, 7, 10, 14 to evaluate the role of DC in dissemination of HIV-1. iDC and mDC were preincubated with anti-DC-SIGN monoclonal antibody（McAb） and/or anti-ICAM-3 McAb before HIV-1 stimulation to find the effects of the two antibodies on DC transmission of HIV-1. Results The level of p24 antigen in coculture supernatant of iDC stimulated by M-tropic HIV-1 and mDC stimulated by M- and T-tropic HIV-1 increased and was significantly higher than that of the controls （ P = 0.001 ）. The upregulated level of p24 antigen in coculture supernatant of T-tropic HIV-1-stimulated iDC was not observed in controls. The level of p24 antigen decreased in supemat ants of iDC primed with M-tropic HIV-1 and mDC primed with M- or T-tropic HIV-1 after preincubation with anti-DC- SIGN McAb, but not with anti-ICAM-3 McAb. Conclusion iDC may play a role in the transmission of HIV-1 with M-tropic, but not T-tropic HIV-1 transmission, mDC may transmit both M-tropic and T-tropic HIV-1 to CD4^＋T cells. The inhibition of HIV-1 transmission by anti-DC-SIGN McAb showed that DC-SIGN may facilitate HIV-1 dissemination from DC to T cells.
作者 耿文清 尚红 姜拥军 刘静 王亚男 苏艳丽 张子宁 韩晓旭 刁莹莹 代娣 张旻
机构地区 中国医科大学附属第一医院卫生部艾滋病免疫学重点实验室
出处 《中华微生物学和免疫学杂志》 CAS CSCD 北大核心 2007年第7期607-611,共5页 Chinese Journal of Microbiology and Immunology
基金 国家重点基础研究发展计划(973计划 2006CB504206) 国家自然科学基金(30400383) 教育部博士点专项(20040159005)
关键词 HIV-1 树突状细胞 M嗜性毒株 T嗜性毒株 DC—SIGN HIV-1 Dendritic cells（DC） M-tropic strain T-tropic strain DC-SIGN
分类号 R392 [医药卫生—免疫学]
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参考文献19

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中华微生物学和免疫学杂志
2007年 第7期

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