T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis.
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.
Brenchley
Jason M
JM
Human Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hill
Brenna J
BJ
Ambrozak
David R
DR
Price
David A
DA
Guenaga
Francisco J
FJ
Casazza
Joseph P
JP
Kuruppu
Janaki
J
Yazdani
Javaidia
J
Migueles
Stephen A
SA
Connors
Mark
M
Roederer
Mario
M
Douek
Daniel C
DC
Koup
Richard A
RA
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*
D004279:DNA, Viral; D015683:Gene Products, gag