Background:  Interleukin (IL) -7 plays an essential role in the development and the maintenance of memory CD8⁺ T cells by rescuing them from apoptosis and by homeostatic self renewing. During primary HIV infection, several defects of the HIV-specific T cell response have been described, notably a default in the generation of memory HIV-specific CD8⁺ T cells. Early control of viral replication by HAART preserves some immune responses. In this study, we tested the hypothesis that early initiation of HAART would allow the emergence of HIV-specific CD8⁺ T cells expressing high levels of IL-7Rα, a specific marker of memory cells.

Methods:  We enrolled 28 subjects at the acute phase of primary HIV infection (16 of whom were subsequently treated at this stage) and compared them to 5 HIV controllers (defined as infected for >10 years and with persistent undetectable HIV RNA plasma levels in the absence of any treatment). HIV-specific CD8⁺ T cells were identified by co-staining with 9 HIV HLA class I pentamers and a total of 60 specificities were tested. Phenotypic characterization and CD127 expression was assessed by flow cytometry and proliferation by carboxy-fluorescein diacetate, succinimidyl ester (CFSE) labeling.

Results:  During primary HIV infection, most HIV-specific CD8⁺ T cells co-expressed CD27 and CD45RO (85%±19% and 88±9%, respectively) which corresponds to a transient stage of differentiation. They were highly activated (CD38 80%±20%; HLA-DR 69%±20%) and poorly expressed Bcl-2. They expressed very low levels of IL-7Rα (CD127 13%±14%), which expression correlated positively with that of Bcl-2 and negatively with that of activation markers (p <0.04 for all correlations). After early initiation of HAART, CD127 expression on HIV-specific CD8⁺ T cells increased in treated subjects (from 7%±6% at inclusion to 52%±27% at M24) reaching levels comparable to those observed in HIV controllers (48%±18%). In parallel, these cells acquired a potent proliferative capacity. In contrast, no changes were observed in untreated subjects, neither in CD127 expression (20%±17% at inclusion and 24%±7% at M24) nor in proliferative potential.

Conclusions:  During primary HIV infection, HIV-specific CD8⁺ T cells expressed low levels of CD127 and had few proliferative capacities. Early treatment increased expression of CD127 and allowed HIV-specific proliferation. These results strengthen the hypothesis that an early control of the viremia allows the development of an effective memory pool.