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

Jacob T. Minang, Matthew T. Trivett, Diane L. Bolton, Charles M. Trubey, Jacob D. Estes, Yuan Li, Jeremy Smedley, Rhonda Pung, Margherita Rosati, Rashmi Jalah, George N. Pavlakis, Barbara K. Felber, Michael Piatak, Mario Roederer, Jeffrey D. Lifson, David E. Ott, Claes Ohlen

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)315-326
Number of pages12
JournalJournal of Immunology
Volume184
Issue number1
DOIs
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Minang, J. T., Trivett, M. T., Bolton, D. L., Trubey, C. M., Estes, J. D., Li, Y., Smedley, J., Pung, R., Rosati, M., Jalah, R., Pavlakis, G. N., Felber, B. K., Piatak, M., Roederer, M., Lifson, J. D., Ott, D. E., & Ohlen, C. (2010). 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. Journal of Immunology, 184(1), 315-326. https://doi.org/10.4049/jimmunol.0902410