Biology Reference
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not proliferated for 8±10 years might still contain their TREC copy and are
de®ned as recent thymic emigrants ( RTE). TREC proportions also decline with
age and HIV infection ( Douek et al., 1998; Zhang, 1999; Poulin et al., 1999).
The rapid and sustained increase in TREC proportions observed during
HAART in the majority of treated patients is correlated with the naive T-cell
subset increases (Zhang, 1999; Poulin et al., 1999). This increased thymic pro-
duction allows the repertoire of CD4 T cells to rediversify during HAART as
shown by Gorochov and co-workers (Gorochov et al., 1998), thus helping to
rediversify the host defenses. The hypothesis of an improved thymic function
with HAART has, however, recently been challenged. Indeed, because the
TREC proportions provide a good estimate of the peripheral T-cell turnover, a
simple reduction in the intense immune activation observed during the natural
course of the disease might result in a lower loss by conversion to memory T
cells (Hazenberg et al., 2000). Altogether, however, strong evidence shows that
thymic function was not de®nitively altered in the course of the disease and can
help to re®ll the reservoir of naive T cells during HAART.
CORRECTION OF ABNORMAL ACTIVATION OF THE
IMMUNE SYSTEM AND IMMUNE RECONSTITUTION
One of our ®rst observations was a rapid and remarkable reduction in the cell
surface expression of various T-cell activation markers such as human leuko-
cyte antigen ( HLA)-DR, CD38, or CD25, the interleukin ( IL)-2 receptor, both
on CD4 ( Fig. 20.5) and on CD8 T cells after 2 months of virus reduction
(Autran et al., 1997). The proportions of activated T cells signi®cantly de-
creased in parallel to the reduction of the plasma virus load. Other groups re-
ported a similar decrease in soluble markers of immune activation such as the
in¯ammatory cytokines tumor necrosis factor (TNF )-a and IL-6 (Andersson
et al., 1998; Lederman et al., 1998). In addition, a reduction in the Fas/Fas-
ligand cell surface expression was also observed (Sloand et al., 1999). Both
phenomena, reduced Fas expression and TNF-a levels, certainly help reduce
the abnormal rate of cell death observed in HIV infection (Weichold et al.,
1999) and restore normal numbers in the T-cell compartments. They also have
important impacts on other immune cells such as B cells or polymorphonuclear
cells.
These changes occur very early after virus begins to be controlled, both in
the peripheral blood and in the lymphoid tissues (Anderson et al., 1998; Bucy
et al., 1999; Sachsenberg et al., 1998; Tenner-Racz et al., 1998). Reduced
immune activation is also associated with decreased cell surface expression of
various adhesion molecules ( Bucy et al., 1999), which certainly contributes to
allowing cell recirculation. The same observations are made at any stage of the
disease, in primary infection (Carcelain et al., 1999) as well as in chronic HIV
infection.
