The immunological mechanisms expressed by untreated HIV-1 infected long-term nonprogressors (LTNPs), who have the ability to suppress HIV-1 infection while maintaining immune functions, is not well understood. The purpose of this study is to increase understanding of the immune response within this patient population using gene expression profiles. We assess the gene transcript profile of Peripheral Blood Mononuclear Cells (PBMCs) and the cell subset, CD8+ T cells, following HIV-1 gag stimulation. Both cell types were stimulated in vitro with HIV-1 GAG peptides to elicit a virus specific cellular immune response in infected cells of LTNPs versus cells of Normal Donors (NDs). Standard immunological assays, like IFN-γ Elispot, were used to examine specific cellular responses that may correlate with viral suppression by this group of HIV-infected individuals. Microarray analysis demonstrated a significant difference in the gene expression of LTNPs compared to NDs, confirming an immune response towards HIV antigen stimulation. Furthermore gene responses of CD8+ T cells versus PBMCs (GAG vs. R10) within LTNPs showed most of the increase in expression activity occurring in PBMC cells. Functional analysis indicates LTNP PBMCs having significant gene expression in chemokine activity, immune, defense, and inflammatory responses. In contrast, genes expressed by CD8+ T cells were associated with transcription and nuclear genes. Examining Gag stimulated only cell populations showed similar functions. Overall, data suggests differential regulation of gene families by HIV-1 antigens in both cell type populations, suggesting indirect transcriptional effects are associated with multiple cell types reacting to our stimulation conditions. These data are important in the understanding of immunological mechanisms associated with HIV-1 control and protection against disease progression.