Biology Reference
In-Depth Information
Along with CD3
CD4
, a subpopulation of CD3
CD4
ÿ
cells has been noted
to occur as a consequence of ADCC indicating that either masking or down-
modulation of CD4
cell surface receptor in ADCC had taken place.
The ability to induce ADCC is not restricted to NK cells inasmuch as mon-
ocytes/macrophages alone were capable of lysing gpl20-coated target cells in
the presence of anti-HIV antibody (Jewett and Bonavida, 1990; Jewett et
al., 1990; Wright et al., 1988). Hober et al. (1995) have shown that monocytes
from HIV-seropositive individuals have increased spontaneous cytotoxicity and
ADCC relative to HIV-seronegative donors. Furthermore, we have also shown
that monocytes obtained from normal donors are capable of lysing gpl20-
coated autologous CD3
T cells, indicating that this subpopulation, similar to
the NK cells, can contribute to the destruction of CD4
T lymphocytes in HIV-
seropositive individuals.
Other Roles
A study examined the relationship between survival and two cytotoxic immune
functions and ADCC and NK against CMV targets. Cytotoxicity mediated
by PBMC from 39 severely immno-compromised patients was determined. The
®ndings demonstrate that high base-line ADCC was associated with improved
survival and a similar trend was associated with NK activity. High ADCC but
not NK remained signi®cantly associated with a lower risk of death. This ®nd-
ing suggests that ADCC may be an important determinant of disease progres-
sion independent of antiretroviral therapy, CD4 cell count, and HIV RNA
( Forthal et al., 1999).
The critical role of viral determinants in the establishment of high viral loads
is best illustrated by the requirement of an intact nef gene for the development
of AIDS in humans. Nef is a 27±34 kD myristylated protein and is shown to
increase viral infectivity, T-cell activation, CD4 down-modulation, and MHC
class 1 down-regulation (Saksela, 1997). Expression of Nef in cells protects them
from lysis by CTL resulting from down-modulation of HLA. The HLA A and
B, but not C or E, antigens are down-modulated. Interestingly, HLA A and
B are the major MHC class I encoded proteins to present antigen to CTL,
whereas HLA C and E can interact with various inhibitory receptors on NK
cells and can protect these cells against NK (Collins and Baltimore, 1999).
A study investigated the clinical implications of impairment levels of NK
and LAK during HIV-1 infection. The study reveals low NK activity was sig-
ni®cantly associated with higher risk of progression to CD4 T-lymphocyte de-
pression and to death. Likewise, patients with low NK responsiveness to IFN-a
tended to be at higher risk of death. This ®nding suggests that low LAK-cell
activity and low NK-cell responsiveness to IFN-a may be important in the
pathogenesis of HIV infection ( Ullum et al., 1999).
The pathogenesis of AIDS is a complex and prolonged process that is
a¨ected by a variety of co-factors including the abuse of both intravenous and
smoked cocaine. The exact mechanism by which cocaine facilitates this disease
