Clinical Immunological Study Of Chronic Hepatitis C Virus Infection

Hepatitis C is an important infectious disease of human beings and immune response may play an important role in HCV infection.Th0 lymphocytes resemble functionally both Th1 and Th2 lymphocytes.Th1 lymphocytes produce cytokines such as IL-2,IFN-γ,TNF-α,which possess a potent antiviral activity.The Th2-type pattern of cytokine secretion(IL-4,IL-5,IL-6,IL-10 and IL-13)is able to activate mainly B cells and inhibit Th1 type immune responses.We detected Th1/Th2-type pattern cytokines in patients with chronic HCV.We found that IL-2,IFN-γserum levels are similar in hepatitis and cirrhosis group,IL-4,10 serum levels in cirrhosis group are hinger than hepatitis goup,but TNF-αserum level is lower.We also observed the dynamic cytokines secretion changes of six patients with chronic HCV and founded that along with the development of hepatitis,IL-4,IL-10 serum levels increases gradually, IL-2,IFN-γ,TNF-αdecreased gradually but increased in acute episode of chronic HCV infection.In an patient who received peg-IFN-α2a therapy, IL-2,IFN-γ, TNF-αincreased and IL-4,10 decreased.It is supposed that Th1/Th2 imbalance in periphery blood,espeically increased Th2-type pattern cytokines secretion may play an importment role in chronic HCV infection.Cytokines theraphy to rectificate the Th1/Th2 imbalance may be an new strategy of hepatitis C treatment.We also used in situ hybridization method to detect the expression of HCVRNA in liver biopsies of 30 patients with chronic HCV.We founded that HCVRNA positive signals are single or in some hepatic cells,dispersaled in lobuli hepatis.Little positive cells are in or near the necrosis,infiltrated by lymph cells or mononuclear cells.Increased expression of HCVRNA always raisd the hepatic damage. Regulatory T cells are able to suppress HCV-specific T lymphocyte proliferation and cytokine secretion during chronic HCV infection. We wished to address to what extent regulatory T cells exist in the livers of HCV+ individuals, and what the role of such cells might be in disease progression. We analysed the frequency and distribution of FOXP3+ cells, along with CD4+, CD8+ cells, IL-10,TNF-α,IFN-γ,in liver biopsies of 30 patients with chronic HCV and correlated these data with histological parameters. We found that CD4+, CD8+,FOXP3+,IL-10, TNF-α,IFN-γexpressed mainly in portal tract,folliculus lymphaticus and CD8+ expressed predominantly near necrosis area.When liver damage increased, expression of CD8+, FOXP3+,IL-10,TNF-αincreased,but CD4+,IFN-γdid not increased obversiously. Because FOXP3+ expresses specificially in Treg,it is supposed that the ratio of CD4+/CD8+ degradation revealed dysfunction of CD8+T lymphocyte and Treg may play a critical role in intrahepatic immune regulation of chronic HCV infection. Advanced understanding of immune pathogenesis of chronic HCV infection may provide new strategy and treatment to therapy or prevent HCV infection.