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

减毒活疫苗诱导的免疫反应特性研究 猴免疫缺陷病毒(SIV)株可能提供关于 这种疫苗途径诱导的保护性免疫的性质 恒河猴CD8+T淋巴细胞功能的研究 用SIV减毒活毒株SIV239‘nef或SIV239’3免疫 抑制免疫动物体内SIV复制的CD8+T细胞 能够有效地抑制自体体内的SIV复制 SIV感染的CD4+T细胞对SIV复制的抑制作用 未受刺激的CD8+T细胞需要直接接触， 然而，MHC受到限制，CD3刺激的CD8+T细胞产生可溶性 抑制SIV以MHC-非限制性方式复制的因素 通过高达30倍的刺激CD8+T细胞培养上清， 还能够抑制依赖CCR5和CXCR4的复制 HIV-1毒株对同源CTL表位CD8+细胞的刺激作用 诱导分泌抑制SIV复制的可溶性因子ABLE 活化CD8+T细胞产生RANTES、MIP-1a或MIP-1的研究 接种疫苗的动物几乎是受刺激动物的10倍。 然而，对照组动物的CD8+T细胞，添加了 中和这些趋化因子，单独或联合使用 部分阻断SIV和HIV复制的抑制作用 刺激CD8+T细胞产生的因子我们的结果表明 免疫动物CD8+T细胞对SIV复制的抑制作用 与活的减毒SIV菌株一起涉及MHC限制性和 不受限制的机制和MHC-SIV的不受限制的抑制 复制主要是由于RANTES以外的可溶性因素， MIP-1a和MIP-1引用Gauduin M-C，Glickman RL，意思是R，和 强生反相抑制猴免疫缺陷病毒(SIV) 活体免疫猕猴后CD8+T淋巴细胞的复制 减毒SIV J Virol 1998；72：6315-6324

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