Virus-specific lymphokine production differs quantitatively but not qualitatively in acute and chronic hepatitis B infection

Cytokines that are secreted as a response to viral antigen not only have di rect antiviral properties but also crucially influence immune reactions det ermining the outcome of infection. As an advantageous alternative to the st udy of cytokines present in the supernatants of antigen-specific T cell clo nes and lines, we have used ELISPOT assays to determine the number of inter feron-gamma (IFN-gamma)- and IL4-producing cells generated by peripheral bl ood mononuclear cells from patients with acute hepatitis a (AHB) and chroni c hepatitis a (CHB) infection in response to HBcAg in a short-term culture (48 h). In response to HBcAg IFN-gamma was predominantly produced. In contr ast to the results obtained in acute hepatitis B, the typical lymphokine pa ttern in CHB was characterized by a weak or absent antigen-specific IFN-gam ma production. A predominance of IL-4-producing cells was not observed in e ither AHB or CHB. A significant number of IFN-gamma-producing cells was usu ally detectable during phases of viral elimination and the quality of the l ymphokine response seemed to be epitope independent. Comparison of the resu lts obtained in proliferation assays and ELISPOT assays clearly shows that lymphokine production upon stimulation with viral protein is totally indepe ndent of T cell proliferation and more sensitively reflects antiviral react ivity. (C) 1989 Academic Press.