Nef-specific CD45RA+ CD8+ T cells secreting MIP-1β but not IFN-γ are associated with nonprogressive HIV-1 infection

We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.The novel antigen-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.Increasing evidence in humans and in nonhuman primate models of HIV-1 infection indicates that CD8+ T cells play a direct role in controlling or limiting HIV-1 replication. CD8+ T-cell depletion during acute [1] or chronic [2] SIV infection is associated with a significant increase in viral load. CD8+ T cells exert a strong selective pressure on SIV [3] and HIV-1 [4], whereas expression of particular MHC class I alleles correlates with delayed disease progression in HIV-1 infected individuals [5,6]. However, long-term control of HIV-1 disease is achieved only in a minority of infected individuals, and the mechanisms by which CD8+ T cells contain HIV-1 replication remain unclear. Indeed, high frequencies of IFN-γ producing HIV-1-specific CD8+ T cells have been found in nonprogressors (NP) as well as in untreated HIV-1 infected individual with progressive disease [7]. The magnitude of the specific cellular imm