Impact of NK cells on control of HIV infection in humanized BLT mice (P6207)

Abstract

Evidence suggests natural killer (NK) cells can mediate antiviral activity in HIV-infected humans. Here, we sought to investigate whether the level of NK cell activation in primary HIV infection not only influences the NK cell mediated elimination of HIV infected cells, but also affects the longevity and effectiveness of HIV-specific T cell responses. To address this hypothesis, we monitored HIV viral loads and HIV-specific adaptive immune responses in a humanized BLT mouse model of HIV infection, comparing NK cell-depleted and control mice. Depletion was achieved through the use of an anti-NKp46 antibody prior to HIV infection. Proportions of immune cell subsets and viremia were assessed at baseline and then once a week for at least 5 weeks post-infection using flow cytometry and qRT-PCR. We observed that the impact of NK cells on plasma viral loads varied between batches of mice reconstituted with different tissues. One set of NK cell depleted mice displayed a 4-fold increase in viremia as well as decreased levels of T cell immune activation at 3 weeks post-infection. In a second group of mice reconstituted with independent human tissue, NK cell depletion had no significant effect on viral loads. These results suggest that further investigation is warranted to identify factors accounting for an increased control of HIV replication associated with NK cells in some individuals and not others, such as expression of a protective combination of KIR and HLA alleles.