Biology Reference
In-Depth Information
press high levels of CXCR3, whereas TH2 express CCR3 and CCR4; and 3)
only TH2 clones respond with an increase in [Ca
2
] to the CCR3 and CCR4
agonists eotaxin and TARC, whereas only TH1 clones responded to the
CXCR3 agonist IFN-g-inducible protein 10 (Sallusto et al., 1998).
SLAM
SLAM is a glycoprotein of the Ig superfamily which, as a transmembrane
lymphocytic receptor, is constitutively expressed on CD45RO
memory T cells,
a portion of B lymphocytes, and immature thymocytes, and is also rapidly ex-
pressed on naive T and B cells after activation (Aversa et al., 1997; Cocks et al.,
1995). SLAM engagement augments T-cell expansion and INF-g production
independently of CD28, and its signaling is regulated by the SLAM-associated
protein (SAP). SLAM was observed to be up-regulated in human pathologies
including rheumatoid arthritis and multiple sclerosis (Aversa et al., 1997; Cocks
et al., 1995). Recent data have shown that 1) SLAM-expressing CD4
and
CD8
lymphocytes are diminished in HIV infection; 2) SLAM expression on
CD4
lymphocytes of HIV-infected individuals is preferentially associated
with lack of CD7 (CD4
CD7
ÿ
SLAM
); and 3) SLAM engagement aug-
ments IFN-g and reduces IL-10 production by HIV-stimulated PBMC of
HIV-infected individuals (Meroni et al., 1999).
ANTIVIRAL AND IMMUNE MODULATORY EFFECTS OF HAART
THERAPY IN HIV INFECTION
The current HAART, which usually includes a combination of antiretroviral
compounds active on di¨erent viral enzymes, has modi®ed the natural history
of HIV infection. Although none of these compounds are very e¨ective alone,
combinations of two or more drugs have boosted optimism that HIV replica-
tion and disease progression can be controlled. It is nevertheless essential to
underline that HAART is not the cure for HIV infection and that unsolved
virologic, immunologic, and clinical problems are presented by HAART-
treated individuals ( Table 3.5). Particularly e¨ective in controlling the pro-
gression of HIV infection are therapies based on the combination of reverse
transcriptase and protease inhibitors (De Jong et al., 1998; Flexner, 1998). In
this case, HIV replication will be impeded by two di¨erent mechanisms that
will obstruct the action of two diverse viral enzymes ( Richman, 1996). Viral
replication will be potently suppressed as a consequence of these therapies and
the emergence of multiple-resistant viruses will be delayed. Soon after initiation
of HAART therapy, a string of dramatic e¨ects on virologic and immunologic
parameters are observed in the majority of patients (Angel et al., 1998; Kelleher
et al., 1996, 1997; Martinon et al., 1999; Pakker et al., 1997, 1998; Pontesilli et
al., 1999). First of all, it is possible to observe an increase in CD4 cell count. It
is believed that the immediate increase in CD4 cell count that occurs during the
