Biology Reference
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the viral pathogen, and might contribute to the establishment of persistent in-
fection. During PI, expanded HIV-speci®c CTL clones were not only detected
in peripheral blood, but also within lymph node samples taken from the same
patients (Pantaleo et al., 1997a). However, the levels of representation of
several of these clones was shown to be several orders of magnitude lower in
the nodes than in the circulation, both by PCR and by precursor frequency
analysis ( Pantaleo et al., 1997c). This accumulation took place before the
down-regulation of HIV-1 viremia, which is normally associated with the
emergence of virus-speci®c cell-mediated immunity and with the transition be-
tween acute and chronic HIV infection. This is quite counterintuitive, inasmuch
as CD8
T cells are known to home in on sites of high-level viral replication so
they can mediate their cytotoxic function in situ. However, during PI, HIV
replication is focalized within the lymph nodes, resulting in massive localized
accumulation of viral antigens. Lymph nodes are also the anatomic site where
antigen-speci®c cell-mediated immune responses are initiated and matured.
Thus, it was postulated that the high antigen load routinely detected in lymph
nodes during PI resulted in massive stimulation and rapid egress of HIV-
speci®c CTL from that compartment. Although the precise manner by which
this is achieved is currently unknown, this mechanism clearly holds the poten-
tial to shift the equilibrium existing between viral replication and development
of host immune responses in favor of the former.
Pediatric HIV Infection
Vertical transmission represents the most common route via which children and
infants become infected with HIV-1. In many respects, vertical HIV transmis-
sion represents a form of PI, one in which the time of infection and the source
of the infecting virus can be clearly identi®ed. Accordingly, our group and
others have observed transient TCRBV-speci®c expansions of CD8
T cells in
HIV-infected children and infants (Halapi et al., 1996; Silvestri et al., 1996;
Soudeyns et al., 1993) ( Fig. 7.1). As in PI, detailed analysis of the CDR3 layout
revealed a surprisingly important degree of structural conservation, including
CDR3 size restriction and biased beta chain junctional region usage, both of
which are fully consistent with antigen-speci®c selection processes (McHeyzer-
Williams and Davis, 1995; Rock et al., 1994). In fact, a large part of these
CD8
T-cell expansions were comprised of consecutive waves of ampli®ed T-
cell clones exhibiting di¨erential persistence, re¯ecting the complex dynamics of
the T-cell mobilization process associated with cell-mediated immune responses
(Silvestri et al., 1996; Soudeyns et al., 2000b). Expansions of CD8
T cells were
also observed in uninfected children born to HIV-infected mothers, albeit at a
signi®cantly lower frequency (Soudeyns et al., 2000a). In accordance with these
results, children born to HIV-infected mothers are known to mount potent
HIV-speci®c CTL responses that are thought to play an important role in the
prevention of vertical HIV transmission (Cheynier et al., 1992; Rowland-Jones
et al., 1993). Most interestingly, transient expansions of CD4
T cells, which
