Immune Dysregulation and T-Cell Activation Antigens in HIV Infection - Cellular Aspects of HIV Infection - page 37

pansion of CD8 CD28 ÿ ,CD8 CD38 , and CD8 CD45R0 was also shown
to be present in HIV-infected patients enrolled in a longitudinal study; these
changes were suggested to be at least partially responsible for the functional de-
fects of CMI that are characteristic of HIV infection (Choremi-Papadadopoulou
et al., 1994). Of interest in this context is the observation that CD8 CD28 ÿ T
cells were described to function as T-suppressor lymphocytes that can inhibit
the proliferative response of antigen-stimulated CD4 T-helper cells. Finally,
CD4 CD28 T lymphocytes were recently shown to be expanded in HAART-
treated, HIV-infected individuals, and the percentage of CD4 ÿ and CD8-
expressing CD28 T cells was demonstrated to be directly correlated with the
rate of ®rst HIV decay in patients upon initiation of antiretroviral therapy ( Wu
et al., 1999).
CD38
CD38 is a single-chain glycoproteic molecule that catalyzes the formation of
cyclic adenosine diphosphate ribosomes from reduced nicotinamide adenine
dinucleotide (Ferrero and Malavasi, 1997). CD38 is functionally a 45-kD type-
II cell surface molecule involved in lymphocyte homing and, in particular, in
the regulation of lymphocyte adhesion to endothelial cells (Deaglio et al.,
1998). CD38 is also expressed in various human tissues including skeletal and
cardiac muscle ®bers, epithelial cells of bronchial origin, and cells from the
parotis and hepatic sinusoids (Fernandez et al., 1999). The receptor for CD38
on the surface of endothelial cells was recently identi®ed in CD31, a member of
the immunoglobulin gene superfamily, and the interaction between CD31 and
CD38 was shown to stimulate intracellular calcium ¯uxes and the synthesis of
mRNA for an array of cytokines (Deaglio et al., 1998). CD38 is present in
immune cells during hemopoiesis and disappears in resting, mature lympho-
cytes; expression of CD38 in these mature cells is subsequent to activation
(Ferrero and Malavasi, 1997).
Analysis of CD38 expression on lymphocytes has become an important tool
for monitoring patients during HIV-1 infection (Giorgi and Janossy, 1994;
Giorgi et al., 1993, 1994) and has recently been proposed in the follow-up of
HAART-treated individuals. The prognostic value of such analyses is attrib-
uted to the ability of CD38 to closely re¯ect the activation status of the immune
response. The T-cell subset best investigated for CD38 expression is CD8 .
CD38 expression on CD8 T cells is up-regulated at seroconversion and is
subsequently either maintained at a high level by individuals who rapidly
progress to AIDS, or is partially decreased in subjects in the asymptomatic
phase as compared with healthy controls (Giorgi and Janossy, 1994; Giorgi
et al., 1993, 1994; Lenkei et al., 1998). Data from di¨erent studies indicate not
only that the detection of a high proportion of CD8 CD38 T cells predicts
progression to AIDS in HIV-infected adults, but that the prognostic value of
this marker is synergic to that of CD4 T-cell counts (Bo®ll et al., 1996; Lenkei
et al., 1998). These ®ndings have been attributed to the ability of CD38 to mark