CHARACTERIZATN. OF CD8 SUPPRESSOR FACTOR

HIV临床前疫苗开发主协议计划 启动以使NIAID能够提供资源，以加速 开发有前景的疫苗方法。 一些研究者已经 表明CD 8+细胞分泌的可溶性因子可以介导抑制 艾滋病和SIV。 NIAID有兴趣确定这是否 抑制因子活性也可能是保护免受 感染，即，是否预先存在CD8+淋巴细胞， 抑制或减少HIV在CD4+细胞中复制将能够阻断 感染病毒，或者至少会大大减少 病毒复制和疾病。 如果这种抑制活性可以 通过免疫接种，这个问题可以得到解决。 为了 容易评估疫苗产生抑制因子的能力， 然而，该因子首先必须被纯化，因此， 作为蛋白质的抗体和核酸探针来检测mRNA 因为它可以制备，使得可以容易地测定 的因素。 因子本身的测定，而不是目前使用的 生物测定其活性，将大大简化这一研究 现象 承包商应（1）创建或鉴定细胞系， 分泌可溶性CD8+因子，其水平足以定性 分析，（2）以确定是否释放的可溶性因子 抑制HIV或SIV在CD4+淋巴细胞中复制的CD8+淋巴细胞 是一种新的因子，或者是已知细胞因子的另一种活性， 因子，和（3）如果因子被证明是新的，则纯化和 进一步说明该因素。 一旦确定了因子并进行了分析 用于检测其表达的方法被开发出来， 确定该因子是否可以通过免疫诱导，以确定 一种类型的疫苗是最好的诱导因子，并测试 预先存在的分泌抑制因子的CD8+细胞的能力， 提高保护程度，防止艾滋病毒或SIV感染， 预防针

The HIV Preclinical Vaccine Development Master Agreement Program was initiated to enable the NIAID to provide resources to accelerate the development of promising vaccine approaches. Several investigators have shown that a soluble factor secreted by CD8+ cells can mediate suppression of HIV and SIV. NIAID is interested in determining whether this suppressor activity could also be a correlate of protection from infection, i.e., whether the pre-existence of CD8+ lymphocytes that inhibit or reduce HIV replication in CD4+ cells would be able to block infection upon exposure to virus, or at least would dramatically reduce virus replication and disease. If this suppressive activity can be induced by immunization, this question can be addressed. In order to readily evaluate a vaccine's ability to generate the suppressor factor, however, the factor first has to be purified, so that reagents to it such as antibodies to the protein and nucleic acid probes to detect the mRNA for it can be made, making it possible to easily assay for the presence of the factor. An assay for the factor itself, instead of the currently used bioassay for its activity, would greatly simplify the study of this phenomenon. The contractor is expected (1) to create or identify a cell line that secretes the soluble CD8+ factor in levels adequate for qualitative analysis, (2) to determine whether or not the soluble factor released by CD8+ lymphocytes which inhibits HIV or SIV replication in CD4+ lymphocytes is a novel factor or, alternately, another activity of a known cytokine or factor, and (3) if the factor is demonstrated to be novel, to purify and further characterize the factor. Once the factor is identified and assays for detecting its expression are developed, it will be possible to determine if the factor can be induced by immunization, to identify which type of vaccine is best at induction of the factor, and to test the ability of pre-existing CD8+ cells secreting the suppressor factor to increase the degree of protection from HIV or SIV infection afforded by vaccination.