Accessory cell dependent NK cell mediated PBMC IFN-γ production is defective in HIV infection

HCV and HIV infections impair dendritic cell function. We evaluated the impact of HCV, HIV, and HCV-HIV infection on MDC–NK interactions by analyzing CD3 depleted PBMC for NK cell IFN-γ in response to IL-12 or poly (I:C). Purified MDC and NK cells were analyzed for TLR ligand-dependent, MDC-dependent NK activity. In HIV infection, IFN-γ production by CD3 depleted PBMC was reduced in response to poly (I:C), while response to IL-12 was intact in HCV and HIV infections. Poly (I:C) induced activity was dependent on MDC and partially dependent on IL-12, consistent with accessory cell help. In purified MDC–NK co-cultures, MDC dependent NK IFN-γ and Granzyme B was intact in both HCV and HIV infections, while MDC numerical defects were observed in HIV infection. These data indicate that during viral infection with HIV, accessory cell dependent NK function in the periphery is impaired. This impairment may be related to the identified MDC numerical defect.