Biology Reference
In-Depth Information
HIV-infected adults lysed such targets. The ADCC toxicity was shown to be
mediated by NK cells armed in vivo with cytophilic HIV antibodies, and the
number of CD16
NK cells in HIV-infected children was normal. The inability
of PBMC from children to mediate ADCC against CD4
lymphocytes ex-
pressing HIV antigen was speci®c as they lysed HSV-infected ®broblasts in
ADCC and killed HIV-infected HUT78 cells and K562 in NK CMC. The
addition of HIV-seropositive serum to PBMC of children yielded mixed results
with HIV-infected CD4
T cells. Sera from children interfered with ADCC
from adults, suggesting blocking factors. We suggest that the defective ADCC
may contribute to the rapid disease progression often observed in this patient
population.
There have been many postulated mechanisms of CD4 decline in HIV in-
fection as the percentage of infected cells is small compared with the percentage
of cells lysed. A study examined the relationship of the rate of CD4 percentage
decline and circulating HIV viral loads and gp120-directed ADCC. Several
analyses were made in 20 patients. The rate of CD4 percentage decline was
associated with either NK or ADCC activity or circulating HIV-1 RNA. Thus,
the ability to mediate gp120 ADCC, together with a signi®cant viral load, de-
®ne conditions under which CD4 destruction of cells may occur (Skowron et
al., 1997).
We found that NK e¨ector cells can mediate ADCC against HIV-coated
CD4
tumor target cells (Jewett and Bonavida, 1990; Katz et al., 1987), autol-
ogous CD4
T-cell blasts (Hober et al., 1995; Katz et al., 1987), and gp120-
coated circulating CD4
T lymphocytes (Jewett and Bonavida, 1996). These
®ndings demonstrate that AIDS e¨ector cells can mediate lysis of CEM (CD4
T-cell line) coated with HIV protein in the presence of HIV-speci®c antibody.
Lysis was speci®c, as non-HIV-coated CEM or the addition of HIV-negative
serum resulted in no lysis. We then examined HIV-coated peripheral blood-
derived CD4
T lymphocytes as targets in ADCC. We demonstrated that, in
the presence of HIV-speci®c antibody, HIV-coated CD4
T lymphocytes serve
as targets for ADCC by NK e¨ector cells from HIV
patients. The lytic activ-
ity obtained with AIDS e¨ector cells was comparable to that obtained with
normal e¨ector cells. These results demonstrate that AIDS e¨ector cells can
mediate ADCC against HIV-coated CD4
T lymphocytes and suggest that
ADCC may play a role in vivo in elimination of CD4
T cells and the patho-
genesis of AIDS.
NK cells after interaction with gp120-coated cells in the presence of anti-
HIV antiserum lose their CD16 surface receptor signi®cantly. This loss of
CD16 is accompanied by a decrease in CD56 surface expression and an in-
crease in CD69, CD25, and CD96 surface expression. On the other hand, the
level of CD3
CD4
T cells is signi®cantly decreased in the ADCC samples
relative to control samples. In contrast to the CD3
CD4
T cells, the frequency
of CD3
CD8
cells is signi®cantly increased in ADCC samples, indicating a
speci®c loss or depletion of CD4
cells in the original CD3
T-cell population.
