Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection.
Natural killer (NK) cells are critical in the first-line defense against viral infections. Chronic HIV-1 infection leads to a perturbation in the NK cell compartment, yet the kinetics of this deregulation and the functional consequences are unclear. Here, we characterized changes in the NK cell compartment longitudinally by multiparameter flow cytometry, starting in acute HIV-1 infection. Acute HIV-1 infection was associated with elevated NK cell numbers, with an expansion of CD3(neg)CD56(dim)CD16(pos) NK cells and an early depletion of CD3(neg)CD56(bright)CD16(neg) NK cells. Ongoing viral replication resulted in a depletion of CD3(neg)CD56(dim)CD16(pos) NK cells with a paralleled increase in functionally anergic CD3(neg)CD56(neg)CD16(pos) NK cells, accompanied by reduced functional activity, as measured by CD107a expression and cytokine secretion. Taken together, these studies demonstrate a sequential impairment of NK cell function with persistent viral replication resulting from a progressive deregulation of NK cell subsets with distinct functional properties.
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, USA.
Galit
G
Alter
Nickolas
N
Teigen
Benjamin T
BT
Davis
Marylyn M
MM
Addo
Todd J
TJ
Suscovich
Michael T
MT
Waring
Hendrik
H
Streeck
Mary N
MN
Johnston
Kyle D
KD
Staller
M Tauheed
MT
Zaman
Xu G
XG
Yu
Mathias
M
Lichterfeld
Nesli
N
Basgoz
Eric S
ES
Rosenberg
Marcus
M
Altfeld
D000208:Acute Disease; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count / Q000379:methods; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D014779:Virus Replication / Q000276:immunology
D015703:Antigens, CD