No Major Differences in the Functional Profile of HIV Gag and Nef-Specific CD8⁺ Reponses between Long-Term Nonprogressors and Typical Progressors

The mechanism explaining the failure of HIV-specific CD8⁺ T cell responses to successfully control HIV replication remains elusive. A total of 83 drug-naive HIV-infected individuals, 27 of whom were long-term nonprogressors (LTNP), was examined. The ability of CD8⁺ T lymphocytes to produce three different cytokines (MIP-1β, TNF-α, IL-2) in response to HIV Gag and Nef peptides and to polyclonal stimuli and the ability of HIV-specific CD8⁺ T cells to expand in vitro were evaluated by multiparameter flow cytometry. In response to polyclonal stimulation, LTNP presented significantly higher levels of several CD8⁺ T cell subsets than progressors. While most patients presented detectable Gag and Nef-specific CD8⁺ responses, no significant differences in any of the CD8⁺ functional T cell subsets were recognized when comparing LTNP and progressors. HIV responses were dominated by cells producing only MIP-1β or TNF-α, being similar in LTNP and progressors. However, expansion of HIV-specific CD8⁺ T cells was more frequent in LTNP than progressors, especially for cells producing MIP-1β. LTNP show higher levels of CD8⁺ responses against polyclonal stimuli than progressors. However, HIV-specific CD8⁺ responses do not differ between them except for a more preserved ability of cells from LTNP to expand in vitro.