| The mechanism of chronic hepatitis B virus (HBV) infection remains unclear. It is considered to be related to immune tolerance of HBV and imbalance of the T helper (Th)1/Th2 subset. It is well known that B7-CD28 T-cell costimulation plays a very important role in preventing from immunologic tolerance, and that interleukin-12 (IL-12), IFN-gamma (IFN-y), interleukin-10 (IL-10) are significant factors to regulate the balance of Thl/Th2 subset. In addition, the mechanism that about 5%~10% of hepatitis B (HB) vaccinees could not produce anti-HBs is not clear utterly. In order to farther clarify the mechanism of HBV persistent infection and offer some grounds for diagnosing, treating and preventing from chronic hepatitis B, we have studied the CD28 molecule expression on T lymphocytes and the serum levels of IL-12, IFN-y and IL-10 in patients with chronic HBV infection and HB vaccine non-responders. Part one:Study of CD28 molecule expression on T lymphocytes and levels of IL-12, IFN-γand IL-10 in patients with chronic HBV infectionWe have studied the CD28 molecule expression on CD4+/CD8+ lymphocytes in peripheral blood lymphocytes (PBL) and the serum levels of IL-12, IFN-y and IL-10 inpatients with chronic HBV infection, and combined with the levels of HBeAg and alanine transferase (ALT) in serums to explore the immunopathological characteristic of chronic HBV infection. CD28 molecule expression on CD4+/CD8+ lymphocytes in PBL was detected by using flow cytometry, and levels of cytokines above-mentioned in serums were determined by enzyme linked immunoassay (ElA) for 112 cases with different levels of HBeAg and ALT in serums and 30 normal controls.It showed that the percentage of CD4+CD28+, CD28+, CD4+ and CD8+ lymphocyte subsets of patients with chronic HBV infection with HBeAg positive/ALT normal was significantly lower than that of normal controls, respectively (27.03%, 44.42%, 29.06% and 27.86% vs 34.35%, 53.68%, 37.37% and 33.00%. all .PO.01). Then the percentage of CD28+ and CD8+CD28+ lymphocyte subsets of cases with HBeAg positive/ALT abnormal (62.15% and 26.69%) and cases with HBeAg negative/ALT abnormal (62.20% and 26.17%) was significantly higher than that of normal controls (53.68% and 19.33%, all P<0.01). The serum levels of IL-12, IFN-y, IL-10 in ALT abnormal groups were also higher compared to the normal levels, respectively (all P<0.01). Otherwise, the percentage of CD8+CD28" subset of all groups of patients (HBeAg positive/ALT abnormal, HBeAg positive/ALT normal, HBeAg negative/ALT abnormal and HBeAg negative/ALT normal) was lower than that of normal controls, and the expression rate of CD28 molecule on CD4+/CD8+ T cells of groups of patients was higher than those of controls.It was concluded that the patients with chronic HBV infection with HBeAg positive and ALT normal were probably at the stage of immune tolerance of HBV, and Thl and Th2 cellular immunity were all concerned with immunopathologic injury of hepatocytes with persistent HBV infection, and the CTL response mediated by CD8+CD28+ lymphocyte subset played an important role in the damage of hepatocytes.In addition, the higher serum level of IL-10 may be associated with the chronicity ofHBV infection, and the lack of CD28 molecule expression on T cells or increasedamount of CD8+CD28" subset was not the main factor possibly.Part two:Study on the relationship between B7-CD28 costimulation/ IL-12,IL-10and non-response to hepatitis B vaccineIn order to quest for the mechanism of immunization failure of HB vaccine by analyzing B7 (CD80, CD86)-CD28 molecule expression and the levels of IL-12 and IL-10, we have isolated peripheral blood mononuclear cells (PBMCs) from 15 HB vaccine responders and 15 non-responders who were adults without HBV infection, and incubated them in the presence of PHA as well as purified recombinant hepatitis B surface antigen (rHBsAg). CD80, CD86 and CD28 molecule expression on PBMCs was detected by using flow cytometry, and levels of cytokines above-mentioned in the super...
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