STOP SIV REPLICATION BY CD8+ T LYMPHOCYTES FROM MACAQUES GIVEN LIVE ATTEN SIV

实时关注 SIV 的猕猴 CD8 T 淋巴细胞可阻止 SIV 复制

• 批准号: 6116546
• 负责人: MC GAUDUIN
• 金额: $ 10.61万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116546
• 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

由减毒活疫苗诱导的免疫应答的表征 猴免疫缺陷病毒（SIV）株可能提供线索， 这种疫苗方法诱导的保护性免疫的性质 研究了恒河猴CD 8 + T淋巴细胞的能力 用SIV减毒活毒株SIV 239 'nef或SIV 239' 3免疫 抑制SIV复制免疫动物的CD 8 + T淋巴细胞 能够有效地抑制SIV在自体 SIV感染的CD 4 + T细胞对SIV复制的抑制 未受刺激的CD 8 + T细胞需要直接接触， 然而，CD 3-刺激的CD 8 + T细胞产生可溶性 抑制SIV以MHC非限制性方式复制的因子 来自刺激的CD 8 + T细胞的上清中， 也能够抑制CCR 5和CXCR 4依赖性的复制， 用同源CTL表位刺激CD 8+细胞也 诱导分泌能够抑制SIV复制的可溶性因子 RANTES、MIP-1a或MIP-1的产生 从刺激的CD 8 + T细胞 免疫动物的免疫力几乎是刺激动物的10倍。 然而，添加抗体， 中和这些 - 趋化因子，单独或组合，仅 部分阻断了可溶性SIV和HIV复制的抑制作用， 我们的结果表明， 来自免疫动物的CD 8 + T细胞对SIV复制的抑制 与减毒SIV活毒株一起， 非限制性机制和MHC非限制性抑制SIV 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 约翰逊RP抑制猴免疫缺陷病毒（SIV） 来自用肝免疫的猕猴的CD 8 + T淋巴细胞的复制 减毒SIV J Virol 1998; 72：6315-6324