Potential Role for HIV-Specific CD38(−)/HLA-DR(+) CD8(+) T Cells in Viral Suppression and Cytotoxicity in HIV Controllers

BACKGROUND: HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38(−)/HLA-DR(+) HIV-specific CD8(+) T cells. Here we examined the role of this subset in HIC status. MATERIALS AND METHODS: We compared CD38(−)/HLA-DR(+) CD8(+) T cells with the classical CD38(+)/HLA-DR(+) activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated. RESULTS: Compared to CD38(+)/HLA-DR(+) cells, CD38(−)/HLA-DR(+) cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134–462] vs 638 [307–747], P = 0.001), higher frequency of polyfunctional cells (15% [7%–33%] vs 21% [16%–43%], P = 0.0003), greater proliferative capacity (0-fold [0–2] vs 3-fold [2]–[11], P = 0.007), and higher cytotoxicity in vitro (7% [3%–11%] vs 13% [6%–22%], P = 0.02). The CD38(−)/HLA-DR(+) profile was preferentially generated in response to low viral antigen concentrations. CONCLUSIONS: These data highlight the role of CD38(−)/HLA-DR(+) HIV-specific CD8(+) T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8(+) subset may be important for vaccine strategies.