Background:
The emergence of SIV-specific CD8+ T cells coincides with declining viremia in monkeys acutely infected with SIV. Antiviral CD8+ T cells may also contribute to immune control in chronically infected animals treated with antiretrovirals (ARVs). We explored these relationships using toxin-conjugated MHC class I tetramers to deplete Gag CM9-specific CD8+ T cells in Mamu-A01+ rhesus macaques infected with a pathogenic strain of SIV.
Methods:
Mamu-A*01+ rhesus macaques were infected with SIVmac239. Gag CM9 (CTPYDINQM) tetramers conjugated to saporin were administered to animals with progressive infection and animals with spontaneous control of viremia to < 10,000 copies/mL. Lymphocyte populations in blood, bronchoalveolar lavage fluid, lymph nodes, colon, and jejunum were enumerated via flow cytometry. Plasma viremia was measured via quantitative RT-PCR.
Results:
Immunotoxin-conjugated CM9/Mamu-A*01 tetramers induced a transient and significant depletion of CM9-specific CD8+ T cells in blood with lesser effects in tissues. This manipulation resulted in viral recrudescence in one animal with spontaneous control of viremia but did not alter the kinetics or magnitude of viremia in other animals during acute or chronic infection, irrespective of treatment with ARVs.
Conclusions:
Immunotoxin-conjugated MHC class I tetramers effectively induced a transient depletion of circulating SIV-specific CD8+ T cells. Our results suggest that CM9-specific CD8+ T cells are important for elite control of viral replication but play a minimal role in the transition from acute to set-point viremia in animals with progressive infection. No evidence was found to support the notion that SIV-specific CD8+ T cells contributed to the reduced viremia observed in animals treated with ARVs.