Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 1, Pages 315-326Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0902410
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Funding
- National Cancer Institute
- National Institutes of Health [N01-C0-12400, HHSN261200800001E]
- NATIONAL CANCER INSTITUTE [ZIABC010350, ZIABC010749] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005019] Funding Source: NIH RePORTER
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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. The Journal of Immunology, 2010, 184: 315-326.
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