Biology Reference
In-Depth Information
F i g u r e 20.2. Pro®les of total and naive CD4 cell reconstitution during HAART as a function of
the disease stage. The slopes of reconstitution are roughly parallel in early and late disease stages.
In contrast, naive CD4 cells show a rapid increase at early stages but a slow and delayed increase at
the AIDS stage. In some rare occasions (< 5%), lack of total CD4 and naive CD4 cell recovery
contrasts with the e½cient suppression of virus replication. Data are calculated from 45 patients
receiving HAART, none of them being drug-experienced, with viral loads successfully controlled
(<200 copies/ml) (Autran et al., 1997; Carcelain et al., 1999; Li et al., 1998; Renaud et al., 1999;
unpublished data).
results were con®rmed by various authors (Lederman et al., 1998; Pakker et al.,
1998), thus strengthening the hypothesis of a preserved capacity to regenerate
naive T cells during HIV infection in adults. Computed tomography con®rmed
the preservation of a thymic tissue in HIV-infected adults and its progres-
sive increase in parallel to naive CD4 T-cell ampli®cation during treatment
(McCune et al., 1998). Direct evidence for a thymic participation and T-cell
regeneration during antiretroviral therapy came from the molecular detection
of markers of thymic origin in these subsets of naive T cells (Douek et al., 1998;
Poulin et al., 1999; Zhang et al., 1999a). Indeed, the DNA episomal circles pro-
duced within the thymus during rearrangements of the T cell receptor (TCR)
segments do not replicate with the cell genome. Their detection in naive CD4 T
cells shows that those cells have not undergone multiple cycles of proliferation
since leaving the thymus: high proportions of the TCR rearrangement exci-
sion circles, or TRECs, are found in the subset of phenotypically de®ned
CD45RA
CD62L
CD4 T cells, although only one-tenth of the phenotypically
de®ned naive CD4 T cells harbor TRECs (Douek et al., 1998). Thus, the rela-
tive proportions of TRECs within the CD4 cell subsets ®ts with the phenotypic
de®nition of naive and memory T cells. Once a naive cell emigrates from the
thymus, it does not proliferate until it encounters a speci®c antigen, and then
converts into a memory T cell. Intervals between two cell cycles in a naive cell
might reach 10 years (Sprent and Tough, 1994): Thus, naive T cells that have
