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Pathogenesis and Immunity

Analysis of Total Human Immunodeficiency Virus (HIV)-Specific CD4+ and CD8+ T-Cell Responses: Relationship to Viral Load in Untreated HIV Infection

Michael R. Betts, David R. Ambrozak, Daniel C. Douek, Sebastian Bonhoeffer, Jason M. Brenchley, Joseph P. Casazza, Richard A. Koup, Louis J. Picker
Michael R. Betts
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113;
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David R. Ambrozak
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113;
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Daniel C. Douek
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113;
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Sebastian Bonhoeffer
Ecology & Evolution, ETH Zurich, CH-8092 Zurich, Switzerland; and
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Jason M. Brenchley
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113;
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Joseph P. Casazza
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113;
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Richard A. Koup
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113;
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Louis J. Picker
Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098
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DOI: 10.1128/JVI.75.24.11983-11991.2001
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ABSTRACT

Human immunodeficiency virus (HIV)-specific T-cell responses are thought to play a key role in viral load decline during primary infection and in determining the subsequent viral load set point. The requirements for this effect are unknown, partly because comprehensive analysis of total HIV-specific CD4+ and CD8+T-cell responses to all HIV-encoded epitopes has not been accomplished. To assess these responses, we used cytokine flow cytometry and overlapping peptide pools encompassing all products of the HIV-1 genome to study total HIV-specific T-cell responses in 23 highly active antiretroviral therapy naı̈ve HIV-infected patients. HIV-specific CD8+ T-cell responses were detectable in all patients, ranging between 1.6 and 18.4% of total CD8+ T cells. HIV-specific CD4+ T-cell responses were present in 21 of 23 patients, although the responses were lower (0.2 to 2.94%). Contrary to previous reports, a positive correlation was identified between the plasma viral load and the total HIV-, Env-, and Nef-specific CD8+ T-cell frequency. No correlation was found either between viral load and total or Gag-specific CD4+ T-cell response or between the frequency of HIV-specific CD4+ and CD8+ T cells. These results suggest that overall frequencies of HIV-specific T cells are not the sole determinant of immune-mediated protection in HIV-infection.

  • Copyright © 2001 American Society for Microbiology
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Analysis of Total Human Immunodeficiency Virus (HIV)-Specific CD4+ and CD8+ T-Cell Responses: Relationship to Viral Load in Untreated HIV Infection
Michael R. Betts, David R. Ambrozak, Daniel C. Douek, Sebastian Bonhoeffer, Jason M. Brenchley, Joseph P. Casazza, Richard A. Koup, Louis J. Picker
Journal of Virology Dec 2001, 75 (24) 11983-11991; DOI: 10.1128/JVI.75.24.11983-11991.2001

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Analysis of Total Human Immunodeficiency Virus (HIV)-Specific CD4+ and CD8+ T-Cell Responses: Relationship to Viral Load in Untreated HIV Infection
Michael R. Betts, David R. Ambrozak, Daniel C. Douek, Sebastian Bonhoeffer, Jason M. Brenchley, Joseph P. Casazza, Richard A. Koup, Louis J. Picker
Journal of Virology Dec 2001, 75 (24) 11983-11991; DOI: 10.1128/JVI.75.24.11983-11991.2001
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KEYWORDS

CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
HIV
HIV Infections
Viral Load

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