Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection

Jonah B. Sacha, Juan P. Giraldo-Vela, Matthew B. Buechler, Mauricio A. Martins, Nicholas J. Maness, Won Chung, Lyle T. Wallace, Enrique J. Leóna, Thomas C. Friedrich, Nancy A. Wilson, Atsunobu Hiraoka, David I. Watkins

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

The precise immunological role played by CD4+ T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental CD8+ cell depletion, elite controlling macaques with set-point viral loads ≤500 viral RNA copies/mL mounted robust Gag- and Nef-specific CD4+ T cell responses during reestablishment of control with ≥54% of all virus-specific CD4+ T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific CD4 + T cells neither recognized nor suppressed viral replication in SIV-infected CD4+ T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific CD4+ T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific CD4+ T cells may contribute directly to elite control by inhibiting viral replication in macrophages.

Original languageEnglish (US)
Pages (from-to)9791-9796
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number24
DOIs
StatePublished - Jun 16 2009

Keywords

  • Antigen processing and presentation
  • HIV

ASJC Scopus subject areas

  • General

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    Sacha, J. B., Giraldo-Vela, J. P., Buechler, M. B., Martins, M. A., Maness, N. J., Chung, W., Wallace, L. T., Leóna, E. J., Friedrich, T. C., Wilson, N. A., Hiraoka, A., & Watkins, D. I. (2009). Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proceedings of the National Academy of Sciences of the United States of America, 106(24), 9791-9796. https://doi.org/10.1073/pnas.0813106106