Distribution persistence and efficacy of adoptively transferred central and effector memory-derived autologous SIV-specific CD8+ T-cell clones in rhesus macaques during acute infection

摘要

Plasma viremia decreases coincident with the appearance of virus-specific CD8⁺ T cells during acute HIV or SIV infection. This finding, along with demonstrations of viral mutational escape from CD8⁺ T-cell responses and transient increase in plasma viremia after depletion of CD8⁺ T cells in SIV-infected monkeys strongly suggest a role for CD8⁺ T cells in controlling HIV/SIV. However, direct quantitative or qualitative correlates between CD8⁺ T-cell activity and virus control have not been established. To directly assess the impact of large numbers of virus-specific CD8⁺ T cells present at time of SIV infection, we transferred in vitro expanded autologous central and effector memory-derived Gag CM9-, Nef YY9- and Vif WY8-specific CD8⁺ T-cell clones to acutely infected rhesus macaques. The cells persisted in PBMC between 4 and 9 days but were not detected in gut-associated lymphoid tissue or lymph nodes. Interestingly, a high frequency of the infused cells localized to the lungs where they persisted at high frequency for more than 6 weeks. While persisting cells in the lungs were antigen reactive, there was no measurable effect on virus load. Sequencing of virus from the animal receiving Nef YY9-specific CD8⁺ T cells demonstrated an escape mutation in this epitope less than 3 weeks post infection, consistent with immune selection pressure by the infused cells. These studies establish methods for adoptive transfer of autologous SIV-specific CD8⁺ T cells for evaluating immune control during acute infection, and demonstrate that infused cells retain function and persist for at least 2 months in specific tissues.