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Journal of Virology, February 2004, p. 1160-1168, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1160-1168.2004

T-Cell Subsets That Harbor Human Immunodeficiency Virus (HIV) In Vivo: Implications for HIV Pathogenesis

Jason M. Brenchley,1 Brenna J. Hill,1 David R. Ambrozak,2 David A. Price,1 Francisco J. Guenaga,1 Joseph P. Casazza,2 Janaki Kuruppu,2 Javaidia Yazdani,3 Stephen A. Migueles,4 Mark Connors,4 Mario Roederer,5 Daniel C. Douek,1 and Richard A. Koup2*

Human Immunology Section,1 Immunology Laboratory,2 Immunotechnology Section, Vaccine Research Center,5 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,4 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 753903

Received 5 August 2003/ Accepted 7 October 2003

Identification of T-cell subsets that are infected in vivo is essential to understanding the pathogenesis of human immunodeficiency virus (HIV) disease; however, this goal has been beset with technical challenges. Here, we used polychromatic flow cytometry to sort multiple T-cell subsets to 99.8% purity, followed by quantitative PCR to quantify HIV gag DNA directly ex vivo. We show that resting memory CD4+ T cells are the predominantly infected cells but that terminally differentiated memory CD4+ T cells contain 10-fold fewer copies of HIV DNA. Memory CD8+ T cells can also be infected upon upregulation of CD4; however, this is infrequent and HIV-specific CD8+ T cells are not infected preferentially. Naïve CD4+ T-cell infection is rare and principally confined to those peripheral T cells that have proliferated. Furthermore, the virus is essentially absent from naïve CD8+ T cells, suggesting that the thymus is not a major source of HIV-infected T cells in the periphery. These data illuminate the underlying mechanisms that distort T-cell homeostasis in HIV infection.

* Corresponding author. Mailing address: Building 40 3504, 40 Convent Dr., National Institutes of Health, Bethesda, MD 20892. Phone: (301) 594-8585. Fax: (301) 480-2779. E-mail: rkoup{at}mail.nih.gov.

Journal of Virology, February 2004, p. 1160-1168, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1160-1168.2004




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