FIG. 3.

Coexpression of PD-1 on Tim-3-positive T cells in chronic HCV infection. Coexpression of PD1 on Tim-3-positive bulk and antigen-specific T-cell populations was examined. Mean values are shown expressed as a percentage of the indicated population. (A) Total CD8⁺ T cells that coexpress Tim-3 and PD1 are rare in uninfected control blood. A significant increase is seen in the doubly positive population in peripheral CD8⁺ T cells in chronic HCV infection (P = 0.0074), which is further increased in the liver compartment (P = 0.0007). (B) A similar pattern is seen for CD4⁺ T cells with respect to the liver compartment (P = 0.0135); however, peripheral populations do not differ significantly from uninfected controls. (C) CMV-specific and (D) HCV-specific populations are shown (percentage of pentamer-positive cells). In the periphery, in chronic HCV infection, the proportion of Tim-3/PD1 doubly positive cells is increased on all antigen-specific CTLs independently of specificity; however, the proportion of doubly positive HCV-specific CTLs is significantly higher than CMV-specific and total CD8⁺ T cells in chronic infection (P = 0.0127). Within the liver compartment, an increase in the level of HCV-specific doubly positive cells compared to that in the peripheral blood was not observed. Error bars represent the standard error of the mean. (E) Representative flow plots of PD-1 and Tim-3 staining on antigen-specific cells from peripheral blood.