CLASS I CONTENT ON CD4 AND CD8 CELLS IS SUBOPTIMAL AMONG PATIENTS WITH CHRONIC HEPATITIS C

CLASS I CONTENT ON CD4 AND CD8 CELLS IS SUBOPTIMAL AMONG PATIENTS WITH CHRONIC HEPATITIS C.
P Kimball, S Verbeke and M Shiffman, Dept. of Surgery, Medical College of Virginia, Richmond, VA.

The ability to resolve a viral infection depends upon the generation of an appropriate cytotoxic T cell (CTL) response. CTL activation depends upon upregulation of surface Class I antigens. We speculated that the inability of CTL's from hepatitis C (HCV+) patients to clear the virus is associated with suboptimal expression of Class I on patient T-cells. To study this hypothesis, we compared Class I expression before and after PHA stimulation using T-cells from 10 normal and 24 chronic HCV+ individuals. All HCV+ patients had elevated serum ALT, biopsy confirmed severe hepatitis and were HCV-RNA positive. Peripheral T-cells were stimulated with the mitogen PHA for 48 hrs. Proliferation was measured by incorporation of tritiated thymidine. Three color flow cytometry was used to calculate Class I expression among T-helper (CD3+CD4+) and T-suppressor (CD3+CD8+) populations. Data is expressed as MESF units (X 10 ⁴) following florescence calibration with Calbrite beads. We detected proliferative and surface antigen anomalies among HCV+ patients. T-cell proliferation was lower among HCV+ relative to Normals (stimulation index of 73 " 24 vs 219 " 70, p=.001). Although all CD3+CD4+ and CD3+CD8+ cells expressed Class I, the relative content of Class I antigen was significantly lower among HCV+. Class I content on resting T-cells was lower for HCV+ than Normals ( 91 " 3 vs 333 " 79 MESF, p<.0002) (resting helper vs suppressor levels, p=ns). PHA activation increased the disparity between HCV+ and Normal cells. Class I content on activated T-helper cells from HCV+ versus Normal was 556 " 144 vs 1,318 " 551 MESF ( p<.0001). Class I content on T-suppressor cells from HCV+ versus Normal was 481 " 104 vs 1,060 " 403 MESF (p<.0001). In summary, we have evidence of biochemical and proliferative insufficiency among T-helper and suppressor populations from HCV+ individuals which may contribute to cellular inability to eradicate HCV viral infection.