Biology Reference
In-Depth Information
activation of the immune system in possible correlation with disease progres-
sion. Moreover, some of the CD8
CD38
lymphocytes display cytotoxic
activity against viral antigen-expressing CD4
T cells, possibly contributing to
CD4
T-cell depletion ( Ho et al., 1993). More recently, other studies have
shown that the presence of a high proportion of CD8
CD38
T cells predicts
the subsequent decline of CD4
T-cell counts (Bo®ll et al., 1996). Additionally,
cross-sectional studies showed that CD8
CD38
T cells correlate with increased
titers of HIV plasma viremia in subjects treated with HAART ( Burgisser et al.,
1999), and to lack of response to therapy in children who are enrolled in anti-
viral protocols (Vigano et al., 1998). The prognostic value of CD38 expression
on CD8
may be further improved by evaluating the co-expression on these
cells of CD45RO. Thus, the relative proportion of CD8
CD45RO
CD38
T cells is predictive of CD4 cell decline, whereas the percentage of the
CD8
CD45RA
CD38
population is not (Kestens et al., 1994). These ®ndings
may be explained by the observation that CD8
CD45RA
T cells constitu-
tively express CD38 even in normal controls and thus o¨er no signi®cant con-
tribution to the prognosis. On the contrary, CD8
CD45RO
T cells express
CD38 only upon cell activation, therefore rendering CD38 a good marker in
evaluating activated T cells within the CD45RO
subset. In addition to ex-
pressing CD45RO
CD38
, the majority of CD8
antigen-speci®c T cells of
HIV-infected individuals express major histocompatibility complex (MHC)
class II antigens ( Ho et al., 1994). Analysis of sorted populations of CD8
cells
de®ned by HLA-DR and CD38 expression showed that the population that
expressed both HLA-DR and CD38 had the strongest CTL activity, the HLA-
DR
CD38
ÿ
and HLA-DR
ÿ
CD38
populations had intermediate CTL
activity, and, ®nally, the double-negative cells had very little activity ( Ho et al.,
1994). Furthermore, in HIV infection, the percentage of CD8
CD38
T cells
was observed to correlate with the defective proliferative response of mitogen-
stimulated T cells. The expression of CD38 on CD4
T cells has been analyzed
less thoroughly, but CD38 can also be up-regulated in this lymphocyte subset
( Benito et al., 1997). CD4
CD38
cells were found to rarely be increased dur-
ing primary HIV-1 infection whereas this subset can be upregulated during the
chronic phases of the disease. These cells were shown to mostly express HLA-
DR in addition to CD38. This increase in CD38 expression correlates with the
decline in CD4
T cells (Benito et al., 1997). It has also been proposed that the
increase in the percentage of CD4
T cells that express CD38 at the late stages
of the disease is a predictor of death.
CD95 (Fas)
CD95 (Fas antigen) is a protein expressed on the surface of lymphocytes
(Miyawaki et al., 1992). Activation of Fas by its ligand ( FasL) can activate
T-cell proliferation and cytokine production or can induce apoptosis in sus-
ceptible cells (Suda et al., 1993). This system is ®nely regulated, as it was shown
that a soluble form of Fas (sAPO-1/Fas) can prevent the interaction between
