Different quality of HIV-1 GAG P24 specific T cell response between viraemic controllers and progressors

Abstract

Immune correlates of protection against HIV infection are crucial for a successful HIV-1 vaccine development. Study in a unique group of infected individuals who are able to control HIV naturally (HIV controllers; HIV load less than 2,000 copies/ml without antiretroviral therapy) have provided us a chance to investigate the role of host immune responses in HIV protection. In this study, the functional quality of HIV-1 Gag p24-specific-CD8⁺ T cell responses on HIV-1 control were assessed and compared between the groups of clinically distinct HIV-1 infected individuals, viraemic controllers (VC, pVL < 2,000 copies/ml) and typical progressors (TP, pVL > 2,000 copies/ml) to determine their impacts on natural HIV-1 clinical outcome. The functional quality of specific-CD8⁺ T cell responses was defined as the number of function simultaneously performed (from single to full 5 functions of IL-2, TNF-α, IFN-γ, MIP1-β and CD107a expression). In agreement with previous study, HIV-1 Gag p24-specific-CD8⁺ T cell responses of VC were composed of higher functional quality CD8⁺ T cells than that of TP (p < 0.05). This high functional quality of HIV-1 Gag p24-specific-CD8⁺ T cell responses observed in VC were independent of age, duration of HIV-1 infection or even presence of protective HLA-I alleles (HLA-B*27, -B*57 and –B*58) and were observed at both a whole p24 protein specific and a single epitope specific level. Moreover, the absolute number of high functional quality HIV-1 Gag p24-specific-CD8⁺ T cells was significantly in a negative correlation with pVL (r = -0.6984, p = 0.0006) and also in a positive correlation with CD4⁺ T cell count (r = 0.5648, p = 0.0095), hence clearly illustrated their roles in determining HIV-1 clinical outcome. In conclusion, this study indicated that possession of an adequate numbers of high functional quality HIV-1 p24-specific-CD8⁺ T cells is important in order to become a natural HIV controller and provided a solid evidence supporting their roles as an immune correlate of HIV-1 protection. The information obtained from this study will pave the way toward a successful HIV-1 T-cell based vaccine in the near future.