LIVE ATTENUATED SIV IMMUNIZATION: TYPE1 T HELPER RESPONSES & ENHANCED CHEMOKINE

SIV 减毒活疫苗接种：1 型 T 辅助者反应

• 批准号: 6313037
• 负责人: MC GAUDUIN
• 金额: $ 9.62万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-06-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6313037
• 关键词: AIDS; Mammalia; communicable diseases; immunology; inflammation; lymphatic system; vaccines; virus

Characterization of immune responses induced by live attenuated simian immunodeficiency virus (SIV) strains may yield clues as to the nature of protective immunity induced by this vaccine approach We investigated the ability of CD8+ T lymphocytes from rhesus macaques immunized with the live attenuated SIV strains SIV239'nef or SIV239'3 to inhibit SIV replication CD8+ T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4+ T cells Suppression of SIV replication by unstimulated CD8+ T cells required direct contact and was MHC-restricted However, CD3-stimulated CD8+ T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion by as much as 30-fold Supernatants from stimulated CD8+ T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent HIV-1 strains Stimulation of CD8+ cells with cognate CTL epitopes also induced secretion of soluble factors abl e to inhibit SIV replication Production of RANTES, MIP-1a or MIP-1 from stimulated CD8+ T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8+ T cells of control animals However, addition of antibodies that neutralize these -chemokines, either alone or in combination, only partly blocked inhibition of SIV and HIV replication by soluble factors produced by stimulated CD8+ T cells Our results indicate that inhibition of SIV replication by CD8+ T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1a and MIP-1 REFERENCES Gauduin M-C, Glickman RL, Means R, and Johnson RP Inhibition of simian immunodeficiency virus (SIV) replication by CD8+ T lymphocytes from macaques immunized with live attenuated SIV J Virol 1998; 72:6315-6324

减毒活疫苗诱导的免疫反应的表征 猿猴免疫缺陷病毒（SIV）株可能提供有关 这种疫苗方法诱导的保护性免疫的性质 研究了恒河猴 CD8+ T 淋巴细胞的能力 用减毒活 SIV 毒株 SIV239'nef 或 SIV239'3 进行免疫 抑制免疫动物的 SIV 复制 CD8+ T 淋巴细胞 能够有效抑制自体 SIV 复制 SIV 感染的 CD4+ T 细胞 通过以下方式抑制 SIV 复制 未刺激的 CD8+ T 细胞需要直接接触，并且 MHC 限制 然而，CD3 刺激的 CD8+ T 细胞产生可溶性 以 MHC 不受限制的方式抑制 SIV 复制的因素 多达 30 倍 来自刺激的 CD8+ T 细胞的上清液 还能够抑制 CCR5 和 CXCR4 依赖的复制 HIV-1 菌株还用同源 CTL 表位刺激 CD8+ 细胞 诱导分泌可抑制SIV复制的可溶性因子 从受刺激的 CD8+ T 细胞产生 RANTES、MIP-1a 或 MIP-1 接种疫苗的动物比接受刺激的动物高出近10倍 对照动物的 CD8+ T 细胞 然而，添加抗体 仅单独或组合地中和这些趋化因子 通过可溶性部分阻断对 SIV 和 HIV 复制的抑制 由受刺激的 CD8+ T 细胞产生的因子 我们的结果表明 免疫动物的 CD8+ T 细胞抑制 SIV 复制 减毒活 SIV 毒株涉及 MHC 限制性和 不受限制的机制以及 MHC 对 SIV 的不受限制的抑制 复制主要是由于 RANTES 以外的可溶性因子， MIP-1a 和 MIP-1 参考文献 Gauduin M-C、Glickman RL、Means R 和 Johnson RP 抑制猿猴免疫缺陷病毒 (SIV) 来自用活疫苗免疫的猕猴的 CD8+ T 淋巴细胞的复制 减毒 SIV J Virol 1998； 72:6315-6324