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

Human Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Journal of Virology (Impact Factor: 4.44). 03/2004; 78(3):1160-8. DOI: 10.1128/JVI.78.3.1160-1168.2004
Source: PubMed


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.

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Available from: Brenna Hill, Apr 10, 2014
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    • "Another example of an advance enabled by cell separation is the isolation of HIV-infected WBCs from patients (Pitcher et al 1999, Douek et al 2002, Brenchley et al 2004) for individual testing; these developments have provided essential insight into the pathology of HIV, leading to better treatment and management of the disease. "
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    • "Among CD4 + T cells, three large populations exist: naive CD4 + T cells, memory CD4 + T cells, and terminally differentiated memory CD4 + T cells (Brenchley et al., 2004a). While all three subsets are infected by the virus in vivo, they do not populate all anatomical sites equally (Brenchley et al., 2004b) and are not equally infected (Brenchley et al., 2004a), with memory CD4 + T cells residing within the gastrointestinal (GI) tract infected most frequently (Brenchley et al., 2004b; Mattapallil et al., 2005). Memory CD4 + T cells are thought to live for decades (Combadiere et al., 2004) and thus represent a very long-lived population of target cells for the virus. "
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