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F i g u r e 12.2. In¯uence of HAART on the expression of activation markers and priming for
apoptosis in peripheral lymphocytes from HIV-infected persons. (A) Three representative patients
have been followed for the ex vivo expression of the activation markers (lines) and spontaneous
( gray bars) or anti-CD3-induced apoptosis (hatched bars) in CD4 T cells at initiation (M0) or after 6
months (M6) of HAART treatment. HAART induces a strong decrease of both activation markers
and spontaneous and activation-induced apoptosis. (B) 18 months follow-up of the susceptibility to
spontaneous apoptosis of memory (CD45R0
) and activated (HLA-DR
) lymphocytes from three
representative patients. In addition to decrease the expression of activation markers, HAART in-
duces a relative normalization of the intrinsic fragility of activated lymphocytes.
restore cytokine synthesis. This was done at the single-cell level by the intra-
cellular detection by ¯uorescence-activated cell sorter (FACS) analysis of cyto-
kines produced by CD4 and CD8 T cells in response to the polyclonal activation
PMA ionomycin. Concerning the restoration of IL-2 synthesis, it appeared
that HAART induces a progressive increase in the percentage and absolute
number of IL-2-producing CD3 T cells, as illustrated on the dot plots shown in
Figure 12.3A. However, only an incomplete restoration of IL-2 synthesis was
observed after 18 months of HAART, and analysis of IL-2 production by naive
and memory T-cell subsets revealed that this was due to the altered capacity of
naive CD4 T cells from these patients to produce IL-2 ( E. Ledru et al., un-
published data). These observations raise the question of the functionality of
the naive CD4 subset that emerges under HAART. Concerning IFN-g syn-
thesis, the normal proportions of IFN-g producers before treatment slightly
decreased after HAART (Fig. 12.3A). In contrast, we found that HAART is
associated with an altered homeostasis of TNF-a producers. Indeed a progres-
