Proliferative Suppression and Class I Insufficiency on Peripheral Blood Cells from Hepatitis C Patients Overcome by Exogenous Cytokines or High-Dose Mitogen

An abnormal T cell response to HCV viral infection is speculated to cause viral persistence, although the mechanism(s) is not understood. Using a classical in vitro test of T cell vigor, proliferative responses to PHA were determined in PBLs from 92 HCV+ individuals and 35 healthy noninfected controls. In addition, since HLA antigens modulate proliferation, surface HLA content was measured by quantitative flow cytometry. The proliferative response of cells from HCV+ individuals was lower than that of controls (SI of 91 ± 70 vs 219 ± 70, P < .0001). In addition, class I content was underexpressed on cells from HCV+ individuals (4540 ± 1359 vs 13,180 ± 5511 MESF units, P < .0001) after 5 days of PHA stimulation. Class II content was also lower than that of controls (89 ± 17 vs 124 ± 61 MESF units, P < .0001) after PHA stimulation. Treatment of cells from HCV+ individuals with a high dose of PHA corrected proliferative hyporesponsiveness (P < 0.01) and class I and II insufficiency (P = 0.02). Treatment with exogenous IL-2 or IFN-γ corrected proliferative reduction (P < 0.01) but not HLA antigen content (P = ns). The results show a biochemical and functional abnormality in PBLs from HCV+ individuals, which may contribute to HCV chronicity.