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

• Published in: The Journal of immunology (1950) 2010-01, Vol.184 (1), p.315-326
• Main Authors: Minang, Jacob T, Trivett, Matthew T, Bolton, Diane L, Trubey, Charles M, Estes, Jacob D, Li, Yuan, Smedley, Jeremy, Pung, Rhonda, Rosati, Margherita, Jalah, Rashmi, Pavlakis, George N, Felber, Barbara K, Piatak, Michael, Jr, Roederer, Mario, Lifson, Jeffrey D, Ott, David E, Ohlen, Claes
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Base Sequence; CD8-Positive T-Lymphocytes - immunology; Chemotaxis, Leukocyte - immunology; Clone Cells; DNA, Viral - genetics; Epitope Mapping; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Flow Cytometry; Immune Evasion - genetics; Immunologic Memory; Lymphocyte Activation - immunology; Macaca mulatta; Molecular Sequence Data; Mutation; Polymerase Chain Reaction; Simian Acquired Immunodeficiency Syndrome - genetics; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; Viremia - immunology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.0902410

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