Biology Reference
In-Depth Information
cluded p58, p70, and ILT2 as well as CD94 and NKG2A. Also, IL-10 upregu-
lates the expression of CD94 in normal CD56
cells, suggesting that the high
level of circulating IL-10 in HIV-infected individuals may be in part respon-
sible for the overexpression of CD94 on NK cells and HIV infections. Although
the expression of KIRs has been examined on NK cells from HIV-infected
individuals, it is important to also investigate the expression of activating re-
ceptors.
Natural cytotoxicity receptors that trigger human NK cell-mediated cyto-
toxicity have been identi®ed and have been called by Moretta et al. (2000)
natural cytotoxicity receptors ( NCRs). They consist of three groups:
1. NKp46 is expressed on all NK cells (both resting and activated) but ab-
sent from other cells tested. Upon crosslinking, it leads to calcium mobi-
lization, cytotoxicity, and cytokine release. NKp46 masking by speci®c
monoclonal antibodies blocks lysis of most target cells.
2. NKp44 is absent in fresh NK but is expressed on IL-2-activated NK cells.
It is absent on T cells and other linkages. Masking of NKp44 by mono-
clonal antibodies partially blocks cytotoxicity.
3. NKp30 cooperates with NKp46 and NKp44 in the induction of cytotox-
icity against a variety of target cells. It is responsible for killing targets not
a¨ected by NKp44 or NKp46. It is expressed on both fresh and activated
NK cells.
Although the expression of NCRs has not been reported in NK from HIV-
infected individuals, the balance between the expression of KIRs and NCRs
and their regulation may be critical for their function and activity against HIV
infection.
Apoptosis of NK Cells in HIV Infection
NK cells undergo both anergy and apoptosis following interaction with normal
or infected target cells. Peripheral blood lymphocytes (PBL) were tested for
functional inactivation of NK cells following ADCC. PBL samples were in-
cubated with gp120 in the absence and presence of anti-HIV antiserum. After
overnight incubation, the cytotoxic functions of the ADCC samples, as well as
control samples, were determined in a 4-h assay using
51
Cr-labeled K562 target
cells. PBL samples that mediated ADCC had considerably less cytotoxic func-
tion when compared with control samples. Likewise, the percentage of frag-
mented DNA was signi®cantly greater in the ADCC samples than in control
samples. The same results were obtained when gp120-coated CD4
CEM and
Jurkat T cells were used as ADCC targets. The addition of IL-2 to the ADCC
samples in the 4-h
51
Cr release assay increased the cytotoxic activity of NK
cells relative to baseline cytotoxicity. The percentage of dead cells in the ADCC
samples was further analyzed with two di¨erent methods, namely, trypan dye
