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Journal of Virology, February 2008, p. 1155-1165, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01275-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Gamma/Delta T-Cell Functional Responses Differ after Pathogenic Human Immunodeficiency Virus and Nonpathogenic Simian Immunodeficiency Virus Infections{triangledown}

David A. Kosub,1 Ginger Lehrman,1 Jeffrey M. Milush,1,{dagger} Dejiang Zhou,1,{ddagger} Elizabeth Chacko,1 Amanda Leone,1,2 Shari Gordon,3,4 Guido Silvestri,3 James G. Else,4 Philip Keiser,1 Mamta K. Jain,1 and Donald L. Sodora1,2*

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas,1 Seattle Biomedical Research Institute, Seattle, Washington,2 Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania,3 Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia4

Received 12 June 2007/ Accepted 7 November 2007

The objective of this study was to functionally assess gamma/delta ({gamma}{delta}) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. {gamma}{delta} 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 V{delta}2 {gamma}{delta} T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of {gamma}{delta} T cells in their peripheral blood than humans did. Following stimulation, {gamma}{delta} 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 {gamma}{delta} T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the V{delta}2+ {gamma}{delta} 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 {gamma}{delta} 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 {gamma}{delta} T-cell dysfunction occurs in HIV+ patients and may contribute to HIV disease progression.

* Corresponding author. Mailing address: Seattle Biomedical Research Institute, 307 Westlake Ave. N., Seattle, WA 98109. Phone: (206) 256-7413. Fax: (206) 256-7229. E-mail: Don.Sodora{at}SBRI.org

{triangledown} Published ahead of print on 28 November 2007.

{dagger} Present address: Department of Experimental Medicine, University of California San Francisco, San Francisco, CA.

{ddagger} Present address: University of California San Diego, San Diego, CA.

Journal of Virology, February 2008, p. 1155-1165, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01275-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Durudas, A., Milush, J. M., Chen, H.-L., Engram, J. C., Silvestri, G., Sodora, D. L. (2009). Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys. J. Virol. 83: 12229-12240 [Abstract] [Full Text]  
  • Ali, Z., Yan, L., Plagman, N., Reichenberg, A., Hintz, M., Jomaa, H., Villinger, F., Chen, Z. W. (2009). {gamma}{delta} T Cell Immune Manipulation during Chronic Phase of Simian HIV Infection Confers Immunological Benefits. J. Immunol. 183: 5407-5417 [Abstract] [Full Text]  


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