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

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 PBMCs between 4 and 9 d, 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 >6 wk. Although persisting cells in the lungs were Ag 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 <3 wk postinfection, 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 mo in specific tissues.