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individual di¨erences in the rate of regeneration and redistribution of CD4
T
cells from the central and peripheral lymphocyte pools ( Douek et al., 1998;
Pakker et al., 1998a, b). Clinical guidelines currently recommended that sub-
jects diagnosed with PI immediately initiate an aggressive regimen of HAART,
using one of several e¨ective combinations of HIV-1 reverse transcriptase and
protease inhibitors ( Ho, 1995). The rationale behind HAART treatment of PI
is three-fold: a) to rapidly suppress viral replication and limit the spreading of
HIV to the peripheral lymphoid compartments; b) to alleviate the symptoms
associated with PI and restore CD4
T-cell counts; and c) to shield initial HIV-
speci®c cell-mediated immune responses against HIV-induced cytopathology
and/or functional impairmentÐit was suggested that these responses might
otherwise become irreversibly compromised during and after PI (Rosenberg et
al., 1997). In this context, TCRBV repertoire analysis revealed that introduc-
tion of HAART during PI in¯uenced the mobilization of T-cell subsets by a)
inducing a more rapid TCRBV repertoire stabilization than that seen in ab-
sence of treatment; b) reducing the global level of T-cell oligoclonality; and c)
initiating a biphasic decline in the peripheral representation of HIV-speci®c
CD8
CTL clones (Soudeyns et al., 2000a). It has been hypothesized that such
progressive reduction in the frequency of HIV-speci®c CTL might eventually
lead to a loss of control over residual levels of HIV replication, but there
has been no evidence so far that this is in fact the case. However, given the
presumed importance of residual replication with respect to the emergence of
drug-resistant variants, the use of immunomodulators, therapeutic vaccines,
and ``structured therapy interruptions'' has been advocated ( Pantaleo, 1997;
Rosenberg et al., 2000).
CONCLUSION
As a result of the somatic gene rearrangement process, each T-cell clone ex-
presses a TCR endowed with uniquely speci®c antigenic recognition properties.
The sum of all TCRs expressed by the host is termed the TCR repertoire, and
it can be analyzed by ¯ow cytometry. HIV-1 infection is characterized by an
unrelenting depletion of CD4
T-helper cells, leading to the progressive ap-
pearance of a lethal state of immunosuppression. The presence of TCR b chain
repertoire perturbations was revealed in various groups of HIV-infected sub-
jects, including HIV-discordant monozygotic twins, patients undergoing pri-
mary HIV infection, and children born to HIV-infected mothers. Although
these studies did not lead to the identi®cation of an HIV-associated SAg, TCR
repertoire analysis was instrumental in the discovery of several fundamental
characteristics of primary antiviral cell-mediated immune responses, including
a) oligoclonal expansion and deletion of antigen-speci®c CTLs; b) transient
polyclonal expansions of CD4
T cells; and c) di¨erential compartmental-
ization of HIV-speci®c CTL. This led to advances in the understanding of the
dynamics of cell-mediated immune responses during acute and persistent viral
