Biology Reference
In-Depth Information
NK CELLS IN HIV INFECTION
Decreased Frequency of Circulating NK Cells and
Phenotypic Alterations
Several reports in the literature have documented that the frequency of circu-
lating NK cells is decreased during human immunode®ciency virus ( HIV ) in-
fection (Landay et al., 1990; Vuillier et al., 1988). However, these ®ndings are
based on the phenotypic expression of surface markers on NK cells as deter-
mined in healthy individuals. The reported de®ciencies in NK numbers in HIV-
infected individuals are primarily based on the identi®cation and enumeration
of circulating NK cells by the NK-associated surface markers CD16 and CD56.
The majority of peripheral blood lymphocytes that mediate NK cytotoxic
activity in healthy adult donors express both the CD16 and CD56 cell surface
molecules ( Lanier et al., 1986). Routinely, the frequency of circulating levels of
NK cells has been obtained with a single surface marker like CD16 or CD56;
in some instances, both markers are used simultaneously. Using these two
NK surface markers, investigators have reported a decrease in NK cell number
in HIV-infected individuals ( Landay et al., 1990; Margolick et al., 1991). Using
the CD56 marker, investigators reported a decrease in both the percentage and
the absolute number of NK cells in HIV-infected individuals (Vuillier et al.,
1988; Mansour et al., 1990). Clearly, studies determining the frequency of NK
cells on the basis of CD16 and/or CD56 expression might be misleading inas-
much as NK cells in HIV
individuals exhibit signi®cant down-modulation of
the CD16 and CD56 markers, and such a population will not be accounted for
in the estimated overall NK cell number.
Our laboratory has examined the expression of both CD16 and CD56 sur-
face markers in HIV-infected individuals (Hu et al., 1995). Three-color ¯ow
cytometry was used to examine the relationship between the CD4
cell num-
bers and the numbers of circulating NK cells as de®ned by the expression of the
CD16 and/or CD56 molecules in control uninfected subjects and in adults
infected with the HIV type 1. The HIV-infected donors had a broad range of
CD4
cell levels, thereby making it possible to correlate the degree of NK cell
numerical de®ciency with progressive stages of HIV-mediated disease including
AIDS. The number and percentage of CD16
CD56
NK cells, the subset that
comprises > 90% of the NK cells in normal adults, was profoundly decreased
in HIV disease even in subjects with high CD4
cell levels. Meanwhile, the
number of CD16
dim=
CD56
ÿ
cells, an NK population that is rare in normal
adults, was elevated (median of 20/mm
3
in uninfected controls and 64/mm
3
in
early HIV disease). Furthermore, not only were many NK cells in HIV-infected
subjects negative for expression of the CD56 molecule by ¯uorescence-activated
cell sorter (FACS) analysis, the majority also expressed reduced levels of the
CD16 molecule. Some CD56
cells and virtually all CD56
ÿ
cells were CD16
dim
.
Functional studies on FACS-sorted cells revealed little NK or ADCC
activity in the CD16
dim
CD56
ÿ
cell population (Hu et al., 1995). The mecha-
