Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication

Thomas C. Friedrich, Laura E. Valentine, Levi J. Yant, Eva G. Rakasz, Shari M. Piaskowski, Jessica R. Furlott, Kimberly L. Weisgrau, Benjamin Burwitz, Gemma E. May, Enrique J. León, Taeko Soma, Gnankang Napoe, Saverio V. Capuano, Nancy A. Wilson, David Watkins

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

"Elite controllers" are Individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. The study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. Here we describe six Indian-origin rhesus macaques that have controlled replication of the pathogenic virus SIVmac239 for 1 to 5 years. To determine which lymphocyte populations were responsible for this control, we transiently depleted the animals' CD8+ cells in vivo. This treatment resulted in 100- to 10,000-fold increases in viremia. When the CD8+ cells returned, control was reestablished and the levels of small subsets of previously subdominant CD8+ T cells expanded up to 2,500-fold above predepletion levels. This wave of CB8+ T cells was accompanied by robust Gag-specific CD4 responses. In contrast, CD8+ NK cell frequencies changed no more than threefold. Together, our data suggest that CD8+ T cells targeting a small number of epitopes, along with broad CD4+ T-cell responses, can successfully control the replication of the AIDS vires. It is likely that subdominant CD8+ T-cell populations play a key role in maintaining this control.

Original languageEnglish
Pages (from-to)3465-3476
Number of pages12
JournalJournal of Virology
Volume81
Issue number7
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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Virus Replication
virus replication
T-lymphocytes
HIV
T-Lymphocytes
Simian immunodeficiency virus
Simian Immunodeficiency Virus
viruses
Viremia
viremia
immunosuppression
Human immunodeficiency virus
natural killer cells
Macaca mulatta
Natural Killer Cells
Population
epitopes
Epitopes
Acquired Immunodeficiency Syndrome
lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Friedrich, T. C., Valentine, L. E., Yant, L. J., Rakasz, E. G., Piaskowski, S. M., Furlott, J. R., ... Watkins, D. (2007). Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication. Journal of Virology, 81(7), 3465-3476. https://doi.org/10.1128/JVI.02392-06

Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication. / Friedrich, Thomas C.; Valentine, Laura E.; Yant, Levi J.; Rakasz, Eva G.; Piaskowski, Shari M.; Furlott, Jessica R.; Weisgrau, Kimberly L.; Burwitz, Benjamin; May, Gemma E.; León, Enrique J.; Soma, Taeko; Napoe, Gnankang; Capuano, Saverio V.; Wilson, Nancy A.; Watkins, David.

In: Journal of Virology, Vol. 81, No. 7, 01.04.2007, p. 3465-3476.

Research output: Contribution to journalArticle

Friedrich, TC, Valentine, LE, Yant, LJ, Rakasz, EG, Piaskowski, SM, Furlott, JR, Weisgrau, KL, Burwitz, B, May, GE, León, EJ, Soma, T, Napoe, G, Capuano, SV, Wilson, NA & Watkins, D 2007, 'Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication', Journal of Virology, vol. 81, no. 7, pp. 3465-3476. https://doi.org/10.1128/JVI.02392-06
Friedrich TC, Valentine LE, Yant LJ, Rakasz EG, Piaskowski SM, Furlott JR et al. Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication. Journal of Virology. 2007 Apr 1;81(7):3465-3476. https://doi.org/10.1128/JVI.02392-06
Friedrich, Thomas C. ; Valentine, Laura E. ; Yant, Levi J. ; Rakasz, Eva G. ; Piaskowski, Shari M. ; Furlott, Jessica R. ; Weisgrau, Kimberly L. ; Burwitz, Benjamin ; May, Gemma E. ; León, Enrique J. ; Soma, Taeko ; Napoe, Gnankang ; Capuano, Saverio V. ; Wilson, Nancy A. ; Watkins, David. / Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication. In: Journal of Virology. 2007 ; Vol. 81, No. 7. pp. 3465-3476.
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