T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis |
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Authors: | Brenchley Jason M Hill Brenna J Ambrozak David R Price David A Guenaga Francisco J Casazza Joseph P Kuruppu Janaki Yazdani Javaidia Migueles Stephen A Connors Mark Roederer Mario Douek Daniel C Koup Richard A |
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Affiliation: | Human Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. |
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Abstract: | 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. Na?ve CD4(+) T-cell infection is rare and principally confined to those peripheral T cells that have proliferated. Furthermore, the virus is essentially absent from na?ve 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. |
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