Activation-induced Cell Death In The Pathogenesis Of Hepatitis B Significance

The significance of activation-induced cell death (A1CD)in pathogenesis of hepatitis BAbstractThe studies in the past have showed that immature thymocytes usually happen apoptosis stimulated by anti-CD3mAb, PHA or Glucocorticoid.In recent years, it has been found that this phenomenon exists also in the mature peripheral blood lymphocytes.The phenomenon that lymphocytes happen apoptosis after activated by stimulation is called activation-induced cell death (AICD). It has been found that 20%?0% reactive T lymphocytes happen apoptosis by homoantigen stimulating again.The phenomenon that lymphocytes happen apoptosis after activation and augmentation is called propriocidal or propriolytic regulation.This regulation may be a physiological mechanism, but may be an immune tolerance mechanism.Cellular immunity is very important in anti-virus infection in the body. Whereas pathogens such as virus have evoluted also some capability against immunity of body. On the one hand , the apoptosis of infectious cells is one of the means of eliminating virus of cellular immunity in the body, on the other hand, virus strive for survival, reproduction and propagation by regulating apoptosis of immunocytes in the body. It has been found recently that some virus such as HIV, HSV-l , LCMV etc can induce apoptosis of lymphocytes. On the one hand the AICD phenomenon may limite excessive immune reaction that may cause body damage, on the other hand the immune tolerace induced by AICD may be an important cause in virus persistent infection.To study AICD phenomenon in lymphocytes and the situation of lymphocyte in virus infection is very necessary to comprehend the mechanism of chronic and severe virus infection.HBV often cause chronic and severeinfection, but the pathogenesis has not been clarified thoroughly.It is veryimportant to clarify the fOllowing problems:Whether HBV can induceperipheral blood lymphocytes apoptosis; Whether there is AICD in HBVinfection; How is the situation of lymphocyte and its subsets in HBVinfection; How is the situation of Th1/Th2 cytokines in HBV infection and itssignificance in AICD. So a series of these problems has been studied in tl1issubject.The main results and conclusions are presented as fOllows:l.The assay of PBMC apoptosis of patients witll hepatitis BTO explore the suitable kind, suitable quantity of inducer of PBMCaPoptosis and suitable time fOr inducing PBMC aPoptosis, it was set up thatvarious inducers in varied quaniity and times induce PBMC apoptosis.It wasfOund that PHA-P was proper to induce AlCD of PBMC and that PBMCcultured with PHA-P l0 ll g /l06 cells fOr 72h was suitable for inducing AICD.To study the singnificance of AlCD in the pathogenesis of chronichepatitis B and chronic severe hepatitis B, the peripheral blood mononuclearcells (PBMCs) were isolated from l4 patients with chronic hepatitis B,6 patients with chronic severe hepatitis B and 10 healthy blooddonors .The PBMCs were cultured with PHA-P for 72 liours in vitro. Thenapoptosis of the PBMCs was assayed by PI staining with flow cytometry .ltwas found that the perceniage of aPoptotic cells of PBMCs in chronichepatitis B group(30.57t l3.43%) was singnificanly higher than that innormaI control group (ll.45 l 5.27% ) (P<0.01)and higher than that inchronic severe hepatitis B group(l3.59 t 6.44%)(P<0.0l). The percentage ofaPoptotic ce1ls of PBMCs in HBeAg(+) hepatitis B group wassingnificanly higher than that in normal control group (29.50 ll2.25%vs11.45 t5.27%, P<0.01). The results show that there are varieddegrees of AICD in varous tires of hepatitis B.lV2.Thc study of PBMC apoptosis induccd by HBV positive seruInTo aPpraise the role of HBV in PBMC aPoptosis, PBMCswere isolated from l0 healthy blood donors. PBMCs from oneperson were devided iflto tWo samples.One sample was cultured with theHBV positive serum.Another sample was cultured with the serum ofhealthy person.After 72 hours incubation, the cells were harvested...