Induction of adaptive regulatory T cells by HIV-infected dendritic cells is defective. (168.15)

Recent studies have shown that dendritic cells (DCs) can induce peripheral conversion of conventional T cells into regulatory T cells (Tregs). DCs are among the first targets of HIV and it is not known whether their infection or exposure to the virus alters their capacity to convert Treg. In our study, 10% of CD3+CD4+CD25-FOXP3- T cells (non-Tregs) expressed FOXP3 5 days after culture with autologous monocyte-derived DCs (moDCs). These converted FOXP3+ cells suppressed proliferation of responder T cells similarly to natural Tregs. In contrast, moDCs from HIV-infected patients were defective at inducing FOXP3 in autologous non-Tregs. MoDCs infected in vitro with a CCR5-using strain were also unable to induce FOXP3. Productive infection of the DC was not required, as DC exposure to inactivated HIV also impaired FOXP3 induction. This defect did not depend on IL-10 or TGF-β, as adding these cytokines did not restore FOXP3 induction. Higher T cell death was observed in infected cocultures than in uninfected ones. Our findings suggest that HIV-infected moDCs kill converted Tregs, leading to a poor induction of adaptive Tregs.