Relationship between T lymphocyte responsiveness and T-helper1/T-helper2 type cytokine release in chronic hepatitis C: a critical reappraisal

Recruitment of virus-specific T lymphocyte subpopulations to liver sites in chronic hepatitis C virus (HCV) infection implies a key role for the immun e response in host-virus interaction. In spite of a multispecific and polyc lonal cytotoxic function exerted by CD8+ lymphocytes, CD4-mediated activity is weak. This allows the infection to persist which in turn is responsible for the development of chronic hepatitis C (CH-C). Such a finding outlines the occurrence of a possible relationship between cytokine (CK) production by CD4 subsets, i.e. T helper (Th)1 or Th2 cells, and the clinical outcome . A prevalence of Th1-derived CK occurs in infected liver, while increased amounts of Th2-related CK are usually found in peripheral blood. Moreover, peripheral blood mononuclear cell (PBMC) cultures from CH-C subjects exhibi t an impaired interferon (IFN)-gamma production and an increase of interleu kin (IL)-12 p70 release after stimulation. The latter pattern seems to be d ue to the enhanced release of IL-12 p40 homodimers, which antagonize IL-12 p70 bioactivity and favour IL-10-induced effects. These results suggest tha t further extensive studies on the imbalance of the CK network at a molecul ar level are required to improve the therapeutical approach in CH-C subject s.