Gamma/Delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections

David A. Kosub, Ginger Lehrman, Jeffrey M. Milush, Dejiang Zhou, Elizabeth Chacko, Amanda Leone, Shari Gordon, Guido Silvestri, James G. Else, Philip Keiser, Mamta K. Jain, Donald L. Sodora

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38 Scopus citations

Abstract

The objective of this study was to functionally assess gamma/delta (γδ) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIY) infection of sooty mangabeys. γδ T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4+ T cells/μl blood) or CD4-low (<200 CD4 cells/μl blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ionomycin or the Vδ2 γδ T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of γδ T cells in their peripheral blood than humans did. Following stimulation, γδ T cells from SIV-positive (SIV +) mangabeys maintained or increased their ability to express the Th1 cytokines regardless of CD4+ T-cell levels. In contrast, HIV-positive (HIV+) patients exhibited a decreased percentage of γδ T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the Vδ2+ γδ T-cell subset which incurred both a decreased overall level in the blood and a reduced Th1 cytokine production. Patients treated with highly active antiretroviral therapy exhibited a partial restoration in their γδ T-cell Th1 cytokine response that was intermediate between the responses of the uninfected and HIV+ patients. The SIV+ sooty mangabey natural hosts, which do not proceed to clinical AIDS, provide evidence that γδ T-cell dysfunction occurs in HIV+ patients and may contribute to HIV disease progression.

Original languageEnglish (US)
Pages (from-to)1155-1165
Number of pages11
JournalJournal of virology
Volume82
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kosub, D. A., Lehrman, G., Milush, J. M., Zhou, D., Chacko, E., Leone, A., Gordon, S., Silvestri, G., Else, J. G., Keiser, P., Jain, M. K., & Sodora, D. L. (2008). Gamma/Delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections. Journal of virology, 82(3), 1155-1165. https://doi.org/10.1128/JVI.01275-07