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-gamma 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.
Kimball
Pam
P
Department of Surgery and Hepatology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia, USA.
Verbeke
Scott
S
Shiffman
Mitchell
M
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D016174:Hepacivirus / Q000254:growth & development / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D010940:Plant Proteins
D016207:Cytokines; D006680:HLA Antigens; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D010940:Plant Proteins; C101135:phytohemagglutinin L protein, Phaseolus vulgaris; D007371:Interferon-gamma