HIV-1-specific CTLs effectively suppress replication of HIV-1 in HIV-1-infected macrophages

Abstract

Both CD4+ T cells and macrophages are major reservoirs of HIV-1. Previous study showed that HIV-1-specific cytolytic T lymphocytes (CTLs) hardly recognize HIV-1-infected CD4+ T cells because of Nef-mediated HLA class I down-regulation, suggesting that HIV-1 escapes from HIV-1-specific CTLs and continues to replicate in HIV-1-infected donors. On the other hand, the CTL recognition of HIV-1-infected macrophages and the effect of Nef-mediated HLA class I down-regulation on this recognition still remain unclear. We show a strong HIV-1 antigen presentation by HIV-1-infected macrophages. HIV-1-specific CTLs had strong abilities to suppress HIV-1R5 virus replication in HIV-1-infected macrophages and to kill HIV-1R5-infected macrophages. Nef-mediated HLA class I down-regulation minimally influenced the recognition of HIV-1-infected macrophages by HIV-1-specific CTLs. In addition, HIV-1-infected macrophages had a stronger ability to stimulate the proliferation of HIV-1-specific CTLs than HIV-1-infected CD4+ T cells. Thus, the effect of Nef-mediated HLA class I down-regulation was less critical with respect to the recognition by HIV-1-specific CTLs of HIV-infected macrophages than that of HIV-1-infected CD4+ T cells. These findings support the idea that the strong HIV-1 antigen presentation by HIV-1-infected macrophages is one of the mechanisms mediating effective induction of HIV-1-specific CTLs in the acute and early chronic phases of HIV-1 infection.