Transfert du VIH des cellules dendritiques aux lymphocytes T : Rôle des anticorps

Dendritic cells (DCs) present on mucosal sites are considered as one of the first HIV target cells following its sexual transmission. The aim of my PhD study was to investigate the early events of the efficient HIV transfer from DCs to CD4 T lymphocytes and to determine the capacity of a panel of NAbs to inhibit in vitro this transfer in primary cells. In the presence of PHA-activated or unstimulated CD4 T- or CD19 B-lymphocytes, the percentage of infected DCs was significqntly increased. This enhancement did not require HIV replication in the target cell, since unstimulated CD4 T- or B-lymphocytes did not support HIV replication. This phenomenon was very specific as we didn’t find an enhancement of HIV replication in DCs when cocultured with CD4 T-cell lines. We found that neutralizing antibodies totally blocked HIV replication in PHA-activated CD4 lymphocytes and partially prevented infection in DCs. To determine if cell-to-cell contact was required for this increased HIV replication in DC, culture membrane inserts were used to physically separate DCs from T lymphocytes, without inhibition of the exchange of HIV particles and secreted cytokines. In the presence of culture membrane inserts, the transmission of virus and the enhancement of DC infection were totally abrogated. Furthermore, when we blocked several cell surface molecules involved in DC-T cell interactions by antibodies (anti-CD3, ICAM-1, anti-CD40), the transfer of HIV and the increase of HIV replication in DCs were impaired, indicating that cell-to-cell contact was necessary for this increased infection in DCs. We found that neutralizing antibody efficiently inhibited HIV transfer from immature DCs to CD4 T lymphocytes. These results suggest that a robust neutralizing antibody response preventing HIV infection and transfer from immature DCs to other permissive CD4 cells should be highly beneficial in protection against sexual HIV transmission. We propose that such antibodies should be induced at the mucosal site by vaccination.