Differential effect of alpha-interferons on CD4- and CD8-positive lymphocytes in chronic hepatitis B virus carriers.

alpha-Interferons are an effective therapy in a proportion of chronic hepatitis B virus (HBV) carriers. The mode of action is almost certainly dependent upon immune modulation in addition to direct antiviral effects but the precise mechanism is unknown. To investigate whether the aberrant T-cell activation present in HBV carriers was responsive to interferons, we have studied the in vitro effect of alpha-interferons on Tac antigen expression and DNA synthesis as early and late markers of T-cell activation, respectively. At a concentration of 1000 U/ml the effect of alpha-interferons on Tac expression was contrasting in the two major T-cell subsets; there was enhancement of Tac expression on CD4-positive T-cells but inhibition of the CD8-positive subset. However, there was no overall effect on lymphocyte proliferation, perhaps as a consequence of the differential effect of alpha-interferons on the early T-cell activation marker. At higher concentration, however, the enhancement of T-cell activation was less clear, indicating that the concentration range that supports T-cell activation is narrow. Such subtle differential effects on T-cell activation may be accompanied by more profound effects on immune function and this may be one way in which alpha-interferons are of value in chronic HBV infection.