[Late spontaneous elimination of HCV-RNA from mononuclear cells derived from peripheral blood in patients with chronic hepatitis C]. / Pózna samoistna eliminacja HCV-RNA z komórek jednojadrzastych krwi obwodowej po skutecznym leczeniu przewleklego zapalenia watroby typu C.

THE AIM: To follow persistence of HCV-RNA in PBMC in patients with chronic hepatitis C (CHC). To estimate the influence of this phenomenon on the cellular immune response of peripheral blood lymphocytes. MATERIAL AND METHODS: 8 HCV-RNA in PBMC positive children, with undetectable serum HCV-RNA after antiviral treatment, have been examined every 2-3 years. The amount of IFN-gamma, IL-12 and IL-18 secreted by PBMC obtained from the children after stimulation with phytohemagglutinin (PHA) was measured. RESULTS: Spontaneous elimination of HCV-RNA from PBMC in 2 to 6 years after treatment was found in all children. In two children HCV-RNA detectable both in serum and in PBMC, without recurrence of hepatitis, was found in single examination. PBMC containing HCV-RNA secreted more IFN-gamma than PBMC lacking it (1221 +/- 458 pg/ml vs. 651 +/- 147 pg/ml; p=0.009, similar correlation was revealed with the regard of IL-12: 21.8 +/- 12.3 pg/ml vs. 5,6 +/- 3,3 pg/ml respectively; p=0.009. Production and release of IL-18 were not correlated with HCV-RNA persistence (p=0.12). CONCLUSION: Patients with CHC and persistence of HCV-RNA in PBMC require longitudinal follow-up in the respect of possible reseroconversion. PBMC containing HCV-RNA reveal enhanced cellular immune response, which most probably effects in spontaneous elimination of the virus.

Impaired induction of cytotoxic T lymphocytes by antagonism of a weak agonist borne by a variant hepatitis C virus epitope.

An epitope that acted as a weak agonist in the cytotoxicity assay was identified as part of the capsid protein of a hepatitis C virus (HCV) variant. In a low concentration, the variant epitope also had a weak antagonistic effect. When a minute amount of this variant epitope was added to the culture for induction, it selectively attenuated the expansion of major cytotoxic T cell populations and drastically reduced the cytotoxic responses against the wild-type epitope. Thus, antagonism to induction suppressed immune responses against both the wild type and the variant, thereby helping the persistence of not only variant itself but also the wild-type HCV. Because this variant was a weak agonist, most cytotoxic T cells induced with the wild-type epitope were cross-reactive with the variant and susceptible to the antagonism to induction. Only the T cells which were not cross-reactive with the variant and not susceptible to the antagonism survived the antagonism in induction. This implied that the specificity of the remaining immune response, if any, was directed exclusively to the wild-type epitope after the emergence of the variant. For viruses like HCV, being heterogeneous itself may contribute significantly toward persistent infection through antagonism to induction.