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腺苷脱氨酶增强负载失活 HIV 的树突状细胞引发的 T 细胞反应。

Adenosine deaminase enhances T-cell response elicited by dendritic cells loaded with inactivated HIV.

机构信息

Hospital Clínic, Barcelona, Spain.

出版信息

Immunol Cell Biol. 2009 Nov-Dec;87(8):634-9. doi: 10.1038/icb.2009.53. Epub 2009 Aug 11.

Abstract

As host immunological defenses are impaired during HIV infection, it is difficult to elicit good responses when attempting to develop therapeutic vaccines against HIV. To try to solve this situation, adjuvants, particularly cytokines, are currently under evaluation. Owing to the fact that adenosine deaminase (ADA) is a member of the family of growth factor with deaminase activity, we tested whether it could improve immune responses in the development of HIV dendritic-cell-based therapeutic vaccines. A co-culture model approach has been used to test the usefulness of ADA as adjuvant. Monocyte-derived dendritic cells from HIV-infected patients were pulsed with inactivated HIV, matured and co-cultured with autologous T cells. Addition of ADA to the co-cultures resulted in enhanced CD4(+) and CD8(+) T-cell proliferation and robust ADA-induced increase in cytokine production (IFN-gamma, TNF-alpha and IL-6). As IFN-gamma, TNF-alpha and IL-6 promote the Th1 versus Th2 phenotype and improve T helper proliferation responses and antigen-specific CTL responses ADA may be considered a promising candidate for therapeutic vaccine adjuvant.

摘要

由于 HIV 感染期间宿主免疫防御受损,因此在尝试开发针对 HIV 的治疗性疫苗时,很难产生良好的反应。为了尝试解决这种情况,目前正在评估佐剂,特别是细胞因子。由于腺苷脱氨酶(ADA)是具有脱氨酶活性的生长因子家族的成员,我们测试了它是否可以改善 HIV 树突状细胞治疗性疫苗开发中的免疫反应。已经使用共培养模型方法来测试 ADA 作为佐剂的有用性。用灭活的 HIV 冲击来自 HIV 感染患者的单核细胞衍生的树突状细胞,使其成熟并与自体 T 细胞共培养。向共培养物中添加 ADA 会导致 CD4(+)和 CD8(+)T 细胞增殖增强,并且 ADA 诱导的细胞因子(IFN-γ、TNF-α 和 IL-6)产生显著增加。由于 IFN-γ、TNF-α 和 IL-6 促进 Th1 与 Th2 表型,改善 T 辅助细胞增殖反应和抗原特异性 CTL 反应,ADA 可被视为有前途的治疗性疫苗佐剂候选物。

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