The Expression And Mechanism Of Circulating Follicular Helper T Cells In Patients With Chronic Hepatitis Diseases

Background: Chronic hepatitis is developed from acute viral hepatitis. The outcomeof acute infection of hepatitis virus is different. The diseases of hepatitis A and E virusinfection is self-limiting, the prognosis is good, generally does not lead to the chronicinfection and cirrhosis. The Chronic hepatitis B infection is a serious wordwide publichealthy problem that caused by hepatitis B virus account for about89%-90%in the variouscauses. However,36%hepatitis C virus infection developed to chronin hepatitis.“Chronichepatitis→liver fibrosis→cirrhosis→liver cancer”is a way of the evolution of liverdisease,threated the survival of patients seriously. Therefore, it is importent to cure thedisease in the initial stage. Current antiviral treatment only inhibit the viral replication, it ismust rely on the cellular immunity and humoral immunity to clear the viral. The cellularimmunity plays an important role in the clearance of HBV, but it also will lead to the liverinjury. If HBV patients can achieve HBeAg and HBsAg serconversion and long-termmaintenance, they will clear the virus thoroughly and prevent its re-invasion. Thisserconversion is achieved by the effect of B-cell-mediated humoral immunity. Humoralimmunity after HBV infection mechanism is unclear, the seroconversion of immune-activehepatitis B patients still rely on the own body’s strength largely.In addition, the innateimmunity and adaptive immune is collaboration in the body’s immune response toanti-HCV infection.The innate immunity will limit the appreciation and spread of virus inthe early infection and though the endogenous and esogenous way tostart the adaptiveimmune response, but it is different to clear the virus completely. The adaptive immuneresponse play an important role in the anti-virus process. However, due to the virusbiological characteristics and host immune function and other factors, this immuneresponse is difficult to clear the virus effectively.Th2cells has been thinked the main cells of T cells to help B cells. Recent studieshave demonstrated that an additional effector subset, follicular helper T (TFH) cells, islargely responsible for B cell help during an immune response, and they located in the apexof the light zone in germinal centers. TFH cells express chemokine receptor CXCR5, whichis critical for their functions, and TFH cells also express ICOS, PD-1, and IL-21, whichprovide excellent markers for identification of TFH cells. TFH cell differentiation, development or related molecular abnormalities will lead to immune dysfunction. So studythe expression of TFH cells in patients with chronic hepatitis have important clinicalsignificance.Obiective: To study the expression and the mechanism of disorders of TFH cells indifferent stages of chronic hepatitis, and explore the functions and regulatory pathways inthe humoral immune. So we can activated the TFH cells though specific manner tomobilize humoral function to clear the hepatitis and establish the dffentive immunesurveillance to prevent the virus from re-invasion.Method: The frequencies of peripheral blood CD4+CXCR5+TFH cells, inducible T cellcostimulator (ICOS), and/or programmed death1(PD-1) positive CD4+CXCR5+TFH cellsin immune-active (IA), immune-tolerant (IT) CHB, and healthy controls (HC) werecharacterized by flow cytometry analysis. The effect of adevofir dipivoxil treatment on thefrequency of CD4+CXCR5+TFH cells, the concentrations of serum IL-2, IFN-γ, TNF-α,IL-4, IL-6, IL-10, IL-21, ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb and HBV loads in IApatients were determined. The potential association of the frequency of CD4+CXCR5+TFHcells with clinical measures was analyzed. In addition, the frequency of splenic and liverCD4+CXCR5+TFH cells in HBV-transgenic mice was examined. At last,he frequencies ofperipheral blood CD4+CXCR5+TFH cells in HCV and SR-HCV were characterized by flowcytometry analysis. The potential association of the frequency of CD4+CXCR5+TFH cellswith clinical measures was also analyzed.Result：1.the frequency of CD4+CXCR5+TFH cells in IA patients was significantlyhigher than that of IT patients and HC.2.Treatment with adefovir dipivoxil reduced thefrequency of CD4+CXCR5+TFH, PD-1+CD4+CXCR5+TFH cells, and the percentages ofCD4+CXCR5+TFH were negatively correlated with HBV DNA.3.Treatment with adefovirdipivoxil reduced the concentrations of IL-2and IFN-γ in drug response patients.4.thefrequency of splenic and liver CD4+CXCR5+TFH cells in HBV-transgenic mice was higherthan that of wild-type controls.5.Higher percentages of peripheral blood CD4+CXCR5+TFHcells were found in SR-HCV and HCV patients as compared with healthy controls.6.Astatistically significant negative correlation was found between the percentage ofCD4+CXCR5+TFH cells and HCV RNA loads.7.No significant difference about theexpression of TFH cells between different types of hepatitis C patients.Conclusion:1.the frequency of CD4+CXCR5+TFH cells in IA patients wassignificantly higher than that of IT patients and HC. and the percentages of CD4+CXCR5+ TFH were positivity correlated with AST. It indicated TFH cells involved in HBV-relatedhumoral immune response and play an important role. Adefovir dipivoxil not only caninhibite HBV viral replication, achieve HBeAg seroconversion, but also significantly reducethe expression of the TFH cells.2.Higher percentages of peripheral blood CD4+CXCR5+TFH cells were found in SR-HCV and HCV patients as compared with healthy controls. Astatistically significant negative correlation was found between the percentage ofCD4+CXCR5+TFH cells and HCV RNA loads. No significant difference about theexpression of TFH cells between different types of hepatitis C patients.3.The subjectunderstanding the expression of TFH cells in different stages of chronic hepatitis. Providingnew ideas for the prevention of hepatitis virus invasion and blockade of chronic hepatitisvirus infection and provide new targets for the treatment of other autoimmune diseases.