Gag- and Nef-specific [CD4.sup.+] T cells recognize and inhibit SIV replication in infected macrophages early after infection

The precise immunological role played by [CD4.sup.+] T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental [CD8.sup.+] cell depletion, elite controlling macaques with set-point viral loads [less than or equal to] 500 viral RNA copies/mL mounted robust Gag-and Nef-specific [CD4.sup.+] T cell responses during reestablishment of control with [greater than or equal to] 54% of all virus-specific [CD4.sup.+] T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific [CD4.sup.+] T cells neither recognized nor suppressed viral replication in SIV-infected [CD4.sup.+] T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific [CD4.sup.+] T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific [CD4.sup.+] T cells may contribute directly to elite control by inhibiting viral replication in macrophages. antigen processing and presentation | HIV