Natural killer (NK) cells play an essential role in the antiviral immune response. Moreover, dendritic cell (DC)-NK crosstalk has been described extensively. However, their role in dendritic cell (DC)-based therapeutic vaccination against HIV remains understudied. Therefore, we aimed to investigate whether DC-based vaccination affects NK cell frequency and phenotype by analysing samples from a previously performed therapeutic vaccination study (Allard et al., Clin. Immunol., 2012).
HIV-1 infected individuals stable on combined antiretroviral therapy (cART), received 4 vaccinations with autologous DCs electroporated with mRNA encoding Tat, Rev and Nef, after which cART was interrupted (ATI). PBMCs were collected at different time points: before vaccination (baselin; N=8), 1 week after second vaccination (vac#2 + 1w; N=9), 4 weeks after ATI (ATI+4w; N=8) and 16 weeks after ATI (ATI+16w; N=8). Phenotyping of NK cells was performed using an extensive flow cytometric panel including inhibitory (KIR2DL1, KIR2DL2/3 and KIR3DL1) and activating receptors (NKG2D and NKp46), immune checkpoint molecules (ICM; PD-1, LAG-3 and Tim3) and receptors involved in homing to the lymph node follicles (CXCR5, CCR7 and CD62L).
We observed that the DC-vaccine induced an increase in the number of cytotoxic CD56dimCD16+ NK cells compared to baseline (median of 4.93% and 1.8%, respectively) whereas the number of non-cytotoxic CD56dimCD16- NK cells decreased (median of 0.8% and 8.03%, respectively). After ATI, the number of CD56dimCD16+ NK cells remained stable (0.4%) and the number of CD56dimCD16- NK cells increased again to even higher levels than at baseline (median of 0.24% at baseline, 0.52% at vac#2+1w, 0.64% at ATI+4w and 1.07% at ATI+16w). Additionally, we observed an overall increase in KIR receptors and CD62L expression whereas a decrease in ICM and CCR7 expression was observed after vaccination. After ATI, an increase in NKG2D and CCR7 was observed which declined again after ATI+16w. Expression of KIR receptors remained stable after ATI+4w and ATI+16w. All ICM were increased after 4 weeks and 16 weeks of ATI, which might be indicative for NK cell activation or even exhaustion in a later stage.
This work shows that our autologous therapeutic DC-vaccine increases the number of NK cells and affects NK cell phenotype. This highlights the importance of NK cells after DC immunotherapy in HIV infection which should be taken into account for future clinical trials.