Murine leukemia virus (MuLV) induced mouse AIDS (MAIDS) is a model system that can be used to study retrovirally-induced immune deficiency. Within this model, CD8+ T cells are the primary effector cell type implicated in the development of resistance to this disease, the same cell type important for resistance to infection and inhibition of disease progression in HIV-exposed or infected individuals. The CD8+ T cell response is a critical facet of the immunologic attack following virus infection, typically mediating the elimination of virus and limiting disease pathogenesis. In mice, several strains of animal are known to possess inherent genetic resistance to the immunodeficiency induced following MuLV infection. Some of the genes controlling this response have been mapped inside the major histocompatibility complex (MHC). However, other strong but unknown gene associations reside outside this region. By comparing the global gene expression profiles of the specific CD8+ T cells induced to respond to MuLV in resistant and susceptible mice, this proposal seeks to identify immune pathways of disease resolution. This research proposal uses DMA microarray techniques to evaluate the differential CD8+ T cell gene response exhibited by C57BL/6 and BALB/c mice, which differ in their inherent vulnerability to an the acquired immunodeficiency syndrome caused by MuLV. To achieve this, the differential gene expression profiles of CD8+ T cells from resistant and susceptible mouse strains will be compared for differences in known immune response genes, as well as new, uncharacterized genes that correlate with disease status. Salient differences in expression will then be independently confirmed and quantified using real-time PCR analysis. The data generated from these studies should shed light on the important immune modulators involved in resistance to acquired immune deficiency in this model system and may suggest clues for mechanisms at play in HIV associated AIDS. ? ?
| Tepsuporn, Suprawee; Horwitt, Jedediah N; Cobb, George W et al. (2008) MAIDS resistance-associated gene expression patterns in secondary lymphoid organs. Immunogenetics 60:485-94 |
