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Journal of Virology, December 2001, p. 11983-11991, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.11983-11991.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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,1,* David R. Ambrozak,1 Daniel C. Douek,1 Sebastian Bonhoeffer,2 Jason M. Brenchley,1 Joseph P. Casazza,1 Richard A. Koup,1 and Louis J. Picker3

Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-91131; Ecology & Evolution, ETH Zurich, CH-8092 Zurich, Switzerland2; and Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Portland, Oregon 97201-30983

Received 3 July 2001/Accepted 17 September 2001

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 naïve 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.

* Corresponding author. Mailing address: Vaccine Research Center, NIAID/NIH, Building 40, Room 3614B, 40 Convent Dr., MSC 3022, Bethesda, MD 20892. Phone: (301) 594-8612. Fax: (301) 480-2779. E-mail: mbetts{at}nih.gov.

Journal of Virology, December 2001, p. 11983-11991, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.11983-11991.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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