INHIB SIV REPLIC BY CD8 T LYMPHOCYTE FROM MACAQUES IMMUNIZD W/ LIVE ATTENUAT SIV

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。 我们 研究了恒河猴CD 8 + T淋巴细胞的能力 用SIV 239弱毒株免疫小鼠，nef还是SIV 239？3 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。 抑制SIV复制 未受刺激的CD 8 + T细胞需要直接接触， MHC限制。 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 高达30倍。 将来自刺激的CD 8 + T细胞的上清液离心。 也能够抑制CCR 5和CXCR 4依赖性的复制， HIV-1病毒株。 用同源CTL表位刺激CD 8+细胞 还诱导能够抑制SIV的可溶性因子的分泌 复制的 从刺激的细胞中产生RANTES、MIP-1 a或MIP-1 a 免疫动物的CD 8 + T细胞几乎是免疫动物的10倍。 来自对照动物的刺激的CD 8 + T细胞。 然而，除了 中和这些α-趋化因子的抗体，无论是单独还是联合 联合使用，仅部分阻断了对SIV和HIV复制的抑制 通过刺激的CD 8 + T细胞产生的可溶性因子。 我们的结果 表明来自人CD 8 + T细胞对SIV复制的抑制 用活的减毒SIV毒株免疫的动物涉及 MHC限制和非限制机制以及MHC非限制机制 SIV复制的抑制主要是由于可溶性因子 除了RANTES，MIP-1a和MIP-1a。

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 able to inhibit SIV replication. Production of RANTES, MIP-1a or MIP-1a 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 a-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-1a.