title: T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis.
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. 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.
authors.affiliation: Human Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Brenna J
authors.initials: BJ
authors.lastname: Hill
authors.forename: David R
authors.initials: DR
authors.lastname: Ambrozak
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Guenaga
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Casazza
authors.forename: Janaki
authors.initials: J
authors.lastname: Kuruppu
authors.forename: Javaidia
authors.initials: J
authors.lastname: Yazdani
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015683:Gene Products, gag / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000821:virology*
chemical_list: D004279:DNA, Viral; D015683:Gene Products, gag