HCV core protein augments cyclosporine immunosuppression.
Hepatitis C viremia occurs universally after liver transplantation. It is speculated that soluble HCV proteins may be immunomodulatory. We measured the effects of HCV core upon human T-cell proliferation, expression of activation markers, and interaction with cyclosporine. Cells were activated with anti-CD3 for 2-6 days. Cultivation with 1, 2, 4, and 8 microg/mL core reduced tritiated thymidine uptake by 7% (P = ns), 63% (P < .001), 69% (P < .001) and 92% (P < .001). Direct cell counting (10(4)) showed proliferative inhibition in treated cultures after 2 days (84%, P < .05), 4 days (93%, P < .05), and 6 days (88%, P < .05). Viability remained greater than 90%. Expression of activation markers was reduced with core treatment. Treatment with 4 microg/mL core for 2, 4, and 6 days reduced CD2+CD25+ by 67% (P < .05), 67% (P < .05), and 51% (P < .05) and CD2+DR+ expression by 54% (P < .05), 46% (P < .05), and 54% (P < .05). Interaction between core and cyclosporine was determined by isobologram analysis which determines whether interactions are synergistic, additive or antagonistic. Combining core with cyclosporine resulted in an additive effect upon proliferative suppression. Linear regression confirmed an additive interaction with an r2 value of 0.98. The data shows that soluble core causes dose dependent suppression of T-cell proliferation and may potentiate suppression by cyclosporine.
Kimball
P
P
Medical College of Virginia Hospitals, Richmond, Virginia 23298, USA. pkimball@gems.vcu.edu
Verbeke
S
S
Shiffman
M
M
D016572:Cyclosporine / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D014758:Viral Core Proteins / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D016572:Cyclosporine