Persistence of viral antigens during chronic hepatitis induces dysfunctional hyporesponsive T cells with increased expression of inhibitory molecules PD-1 and CTLA-4.8, 29, 30 We found that HBV-infected HIS-HUHEP mice had increased numbers of CD3+ T cells in the liver (low dose, 7x; high dose, 6x) and spleen compared with controls (Figure 4A). The gene discussed is CTLA4; the disease is chronic hepatitis.