Biology Reference
In-Depth Information
al., 1998). This correlates with the presence of stronger CTL responses in the
slow progressors as compared with the rapid progressors, thereby indicating the
possibility of selective pressure being exerted by the CTL. Other factors sug-
gested included the presence of secreted molecules that impair CTL responses.
Earlier studies have shown that the tat gene product of HIV is capable of
causing immunosuppression through the induction of TGF-b (Reinhold et al.,
1999), although our experiments show that TGF-b production can be mediated
by responses to HIV independent of Tat. It also induces changes in cells derived
from neural tissues and lymphoid organs (Jurkat cells).
CTL IN HIV-INFECTED INFANTS
Perinatally infected children also show di¨erential progression and pattern of
HIV pathogenesis. Without treatment, 20% of them develop full-blown AIDS
within the ®rst year, whereas most of the rest develop AIDS and die within the
®rst 5 years. Few children go on to develop adult-like disease pattern with slow
progression to AIDS.
The neonatal period is characterized by the abundance of immature lym-
phoid cells including T cells ( Delespesse et al., 1998). The functions of neonatal
T cells have also been reported as less e¨ective than their adult counterparts.
However, some studies have indicated that neonatal T cells are capable of
mounting signi®cant viral-speci®c responses. Indeed, a series of studies of new-
borns that are perinatally infected with HIV has shown the presence of strong
HIV-speci®c CTL directed against the Gag, Pol, and Env proteins (Buseyne et
al., 1998a; Pikora et al., 1997). CTL has been demonstrated in both ex vivo and
in vitro stimulated lymphocyte studies and it was found to be HLA class I re-
stricted. The in vitro CTLs seen in this group were the same as those of an adult
population, whereas the ex vivo CTLs were reported as slightly lower than
those of an adult population. One such study has shown that the presence
of strong HIV-speci®c CTL correlated with children who did not progress to
AIDS within the ®rst year of birth, whereas those who progressed to AIDS
within the ®rst year had lower CTL responses. Although viral load and T-cell
numbers were unrelated to the CTL levels in the ®rst 6 months, they were found
to be related between 7 and 12 months, with lower viral load and higher num-
ber of both CD4
and CD8
cells indicating a possible bene®cial role of CTL
in these infants (Riviere and Buseyne, 1998).
CTL IN HIV-EXPOSED SERONEGATIVE INDIVIDUALS
The exposed seronegative individuals represent a group of individuals who are
repeatedly exposed to the HIV virus but have presumably failed to be infected.
They present an interesting group as they provide a hope for the presence of
a host defense mechanism against the HIV virus that can be exploited in the
