Biology Reference
In-Depth Information
T A B L E 3.3. Alterations of the Fas/Fas Ligand (FasL) and Soluble APO-1/Fas
(sAPO-1/Fas) System in HIV Infection
.
Up-regulation of Fas on lymphocytes of HIV-infected individuals
.
Augmented susceptibility of lymphocyte of HIV-infected individuals to apoptosis
upon ligation of Fas
.
Correlation between expression of Fas/susceptibility of Fas ligation to apoptosis and
clinical stage of HIV infection
.
Monocyte-CD4/Fas-FasL ``kiss of death''
.
CD4-CD8/Fas-FasL ``kiss of death''
.
Reduced serum concentration of sAPO-1/Fas in progressing HIV infection
Fas and FasL thus reducing apoptosis (Cheng et al., 1994). CD95 and its ligand
are expressed at high levels on activated mature lymphocytes, suggesting that
CD95 expression and subsequent cell death may be the physiological conse-
quence of cellular activation. Surface expression of CD95 is increased on lym-
phocytes of HIV-infected individual (Debatin et al., 1994; McCloskey et al.,
1995). Additionally, the interaction of CD95 with its ligand in HIV-infected
cells provokes apoptosis in a high percentage of lymphocytes (Sloan et al.,
1997). Up-regulation of CD95 on monocytes is observed as well in HIV infec-
tion; the augmented expression of CD95 on these cells could be responsible for
the destruction of uninfected CD4 T lymphocytes subsequent to antigenic pre-
sentation and interaction between CD95 (on monocytes) and CD95L (on CD4
cells), via a ``kiss of death'' mechanism (Badley et al., 1997).
Di¨erent experimental ®ndings support a role for the quantitative/qualita-
tive alterations of the CD95/CD95L system in the progression of HIV infection
to AIDS (Table 3.3). These ®ndings include the following:
1. Surface expression of CD95 is augmented in disease progression, and
cells of individuals with AIDS and opportunistic infections express sig-
ni®cantly more CD95 than asymptomatic patients ( Debatin et al., 1994;
McCloskey et al., 1995).
2. Apoptosis induced by engagement of CD95 on the surface of CD4 lym-
phocytes is higher in symptomatic than in asymptomatic HIV-infected
individuals (Baulmer et al., 1996; Soland et al., 1997).
3. The magnitude of anti-CD95-induced apoptosis inversely correlates with
absolute CD4 cell counts ( Bohler et al., 1997a; Soland et al., 1997).
4. Low serum concentrations of sAPO-1/Fas were shown to have a strong
independent predictive power for progression to AIDS in a multivariate
conditional logistic regression model that included, among other vari-
ables, HIV viral load at entry (Medrano et al., 1998).
Another set of results underlines the importance of the CD95/CD95L system
in the progression of HIV infection. Thus, T-helper 1 ( TH1) but not TH2
