CHARACTERIZATN. OF CD8 SUPPRESSOR FACTOR

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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.