Background:  We investigated the in situ localization of simian immunodeficiency virus (SIV)-specific T cells in tissues from SIV-infected macaques during the natural course of infection so this information could serve as the basis for comparison for future vaccine studies. During the course of these studies, we identified localized subpopulations of SIV-specific T cells that apparently down-modulated surface expression of CD8 molecules in B-cell follicles and in vaginal and cervical epithelium.

Methods:  Fresh tissues from SIV_mac239-infected macaques were stained with MamuA01 tetramers loaded with SIV gag, tat, and or an irrelevant peptide. Sections were counterstained with CD8, CD20, or g/d-TCR antibodies. Some sections were triple labeled with tetramers, CD3, and CD8 antibodies. Comparable studies in lymph node sections from an HIV-infected individuals are underway.

Results:  The majority of SIV gag and tat tetramer-stained T cells were localized throughout CD8⁺ zones of all tissues examined and were CD8⁺. In addition, subpopulations of gag and tat tetramer-stained cells that did not stain positive with CD8 antibodies were detected in CD8^­ regions of lymph tissues and largely CD8^­ regions of the vaginal and cervical epithelium. Lymph tissues stained with tetramers and CD20 (B-cell marker) showed tetramer⁺ cells in B cell follicles, indicating that tetramer⁺CD8^- populations of cells in lymph tissues were localized to B cell follicles. Gamma delta TCR antibody staining in lymph nodes showed no colabeling with tetramer stained cells indicating that the tetramer⁺CD8^­ population of cells were not g/d-T cells. Triple labeling with tetramer, and CD3 and CD8 antibodies indicated that tetramer⁺CD8^­ cells were indeed T cells. Negative control staining with tetramers loaded with an irrelevant peptide did not show staining of tetramer⁺CD8^­ cells as seen with virus-specific tetramers indicating that tetramer⁺CD8^­ cells are not natural killer cells non-specifically binding to MHC tetramers.

Conclusions:  We hypothesize that antigen-specific CD8⁺ T cells down-modulate CD8 upon entering B-cell follicles or upon entering the epithelial layer of tissues in macaques, perhaps preventing unwanted cellular lysis and modulating immune activation in these specific tissue locations. Future studies are needed to determine whether this phenomenon also occurs during HIV and other infections.