CHARACTERIZATN. OF CD8 SUPPRESSOR FACTOR

艾滋病毒临床前疫苗开发主协议计划是 启动以使NIAID能够提供资源以加速 开发有前景的疫苗方法。几名调查人员已经 研究表明CD8+细胞分泌的一种可溶性因子可以介导抑制 艾滋病毒和SIV病毒。NIAID有兴趣确定这是否 抑制子活动也可能是一种相关的保护作用 感染，即CD8+淋巴细胞是否预先存在 抑制或减少HIV在CD4+细胞中的复制将能够阻断 在接触病毒后感染，或者至少会显著减少 病毒复制和疾病。如果这种压抑活动能够 通过免疫诱导，这个问题是可以解决的。为了 很容易评估疫苗产生抑制因子的能力， 然而，因子首先必须被提纯，这样对它的试剂才能 作为抗体的蛋白质和核酸探针来检测mRNA 因为它是可以制造的，所以可以很容易地检测出是否存在 这一因素。因子本身的化验，而不是当前使用的 对其活性进行生物测定，将极大地简化这方面的研究 现象。 承包商被期望(1)创建或识别一种细胞系 分泌足够数量的可溶性CD8+因子 分析，(2)确定可溶性因子是否由 CD8+淋巴细胞抑制HIV或SIV在CD4+淋巴细胞中的复制 是一种新的因子，或者，或者，另一种已知的细胞因子或 因子，以及(3)如果因子被证明是新的，则提纯和 进一步确定该因素的特征。一旦确定了因素并进行了分析 为了检测它的表达，将有可能 确定免疫是否可以诱导该因子，以确定哪种 疫苗的类型最好是诱导因子，并测试 预先存在的CD8+细胞分泌抑制因子的能力 提高对艾滋病毒或SIV感染的保护程度 接种疫苗。

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.