Virus-specific CD8 T cells are critical for control of SIV and HIV viral replication. SIV infection in Rhesus macaques (Macaca mulatta) induces SIV-specific CD8 T cells expansion in the blood and multiple tissues. To further evaluate the mechanisms underlying the induction and maintenance of SIV-specific CD8 T cells, we determined the kinetics of SIV-specific CD8 T cells across multiple anatomical sites during acute infection, chronic infection and treatment with anti-retrovirals. Furthermore, we utilized an SIV-gag DNA vaccine to assess the induction of SIV-specific cells upon acute antigen exposure. Finally, we utilized cytomegalovirus (CMV) infected animals to compare the tissue distribution of virus-specific CD8 T cells between two viruses that induce a chronic infection in the host.
Mamu-A*01+ or Mamu-*02+ Rhesus macaques were infected with SIV mac239 or administered with 1 mg of DNA plasmid CMV/R-SIVgag vaccine. CMV infection occurred naturally in the animal facility. SIV-specific CD8 T cells were enumerated and sorted by FACS from the PBMCs, bronchoalveolar lavage (BAL) lymph nodes (LN), liver, spleen, colon and jejunum using MHCI Pentamers. Next generation sequencing of TCR beta genes was performed to determine the clonotypic structure of antigen-specific CD8 T cells across tissues.
Acute SIV exposure induces virus-specific CD8 T cells in peripheral blood and lymph nodes, while chronic viremia seems to be required for expansion in other tissues. This expansion is maintained after administration of antiretroviral therapy, with a tissue resident phenotype most common across the gastrointestinal tract. Finally, natural CMV infection induced CMV specific CD8 T cells predominantly in the PBMCs compared with other anatomical sites.
SIV-specific CD8 T cells can inhabit multiple anatomical sites upon both acute and chronic antigen exposure, with a small fraction developing a tissue-resident phenotype. In comparison, CMV infection induces CMV-specific CD8 T cells primarily in the blood, suggesting distinct tissue distribution between different viruses that induce chronic infection. Clonotypic analysis reveals potential mechanisms involved in development of tissue-specific immunological phenomena during viral infections.