Viral RNA is transferred to pDCs, triggering robust production of IFNs that inhibit HCV replication in hepatocytes. pDCs produce more type I (IFN-α and IFN-β) IFNs, whereas BDCA3⁺ DCs produce more type III IFNs with HCV infection and do not require direct cell-to-cell contact. NK and NKT cells comprise a large proportion of intrahepatic lymphocytes, mediating antiviral functions through a combination of IFN type II (IFN-γ) production and cytolytic function. IFNα-induced TRAIL is associated with the control of HCV (78, 82). Hepatic accumulation of NKp46^hi NK cells is associated with lower viral replication and attenuated fibrosis (78). KCs phagocytose HCV, leading to the induction of innate immune (IFN-β) as well as inflammatory (IL-1β) responses. HCV core protein inhibits type I IFN responses (89) and also drives proinflammatory responses, augmenting processes that result in liver fibrosis (87). IFN-γ induces KC upregulation of Gal-9 and PD-L1, inhibitory ligands that promote T cell dysfunction. LSECs can pinocytose viral particles and produce a broad array of IFNs. Multispecific and polyfunctional CD4⁺ T (Th) cells provide “help” for clonal expansion of B cells and CTLs required for spontaneous viral control. Early expression of CD127, IL-2 production, development of neutralizing Abs, and HCV-specific CTL cells contribute to immune response (148, 149). PD-1 and TIM3 demarcate functionally impaired CTLs. Moreover, CD33⁺ myeloid–derived suppressor cells (150) and FOXP3⁺ Tregs (10, 151) attenuate T cell responses and immune-mediated liver injury.