Poly I:C and STING agonist-primed DC increase lymphoid tissue polyfunctional HIV-1-specific CD8+ T cells and limit CD4+ T-cell loss in BLT mice

Abstract

Effective function of CD8⁺ T cells and enhanced innate activation of DCs in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of the combination of 2´3´-c´diAM(PS)2 and Poly I:C as potential adjuvants capable of potentiating DC´s abilities to induce polyfunctional HIV-1 specific CD8⁺ T-cell responses in vitro and in vivo using a humanized BLT mouse model. Adjuvant combination enhanced TBK-1 phosphorylation and IL-12 and IFN-β expression on DC and increased their ability to activate polyfunctional HIV-1-specific CD8⁺ T cells in vitro. Moreover, higher proportions of hBLT mice vaccinated with ADJ-DC exhibited less severe CD4⁺ T-cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8⁺ T cells in the white pulp from the spleen, reduced spread of infected p24⁺ cells to LN, and with preserved abilities of CD8⁺ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, priming of DC with PolyI:C and STING agonists might be useful for future HIV-1 vaccine studies.

Keywords: CD8+ T cell; dendritic cell; hBLT mouse; lymphoid tissue; vaccine.