Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B: A major factor in activation of the host immune response to the hepatitis B virus

Abstract

The T helper (Th) cell response to hepatitis B core antigen (HBcAg) was analyzed in 76 chronic hepatitis B virus (HBV) carriers with varying degrees of hepatic inflammation and HBV replication. Fifty‐five patients had active viral replication, 28 with minimal histological changes and normal alanine transaminase (ALT) and 27 with active hepatic inflammation and elevated ALT. The remaining 21 chronic hepatitis B surface antigen (HBsAg) carriers had undetectable HBV replication, minimal histological activity, and normal ALT. In addition, 34 chronic HBV carriers were studied prospectively during treatment with α‐interferon. The HBcAg‐specific Th cell response was evaluated by a proliferative assay using 3H‐thymidine uptake and γ‐interferon production by peripheral blood mononuclear cells. The proliferative response and γ‐interferon production of patients with active hepatic inflammation were significantly higher than in patients with minimal histological changes and in controls. In the longitudinal analysis during α‐interferon treatment, 22 of 34 patients sustained an ALT flare accompanied by a parallel, significant Th cell response, which preceded or coincided with the ALT flare. The elevation in the Th cell response and the ALT flare were followed by a significant rise in the serum immunoglobulin (Ig) M anti‐HBc index. Ten of twenty‐two patients with an enhanced Th cell response and an ALT flare seroconverted after α‐interferon treatment. The Th cell activity in the 10 responders rapidly subsided after hepatitis B e antigen (HBeAg) to anti‐HBe seroconversion, whereas in the 12 nonresponders it remained elevated. This study demonstrates that patients with chronic hepatitis B (CAHB) have a detectable and a significant Th cell response to HBcAg, which is likely to be involved in augmenting the immune‐mediated hepatocellular damage and in the activation of HBV‐specific humoral immune reaction. Thus, loss of Th cell nonresponsiveness to HBcAg is an important factor in enhancing the effector immune responses to HBV in chronic hepatitis B. (HEPATOLOGY 1995; 22:1040–1049.).

Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia

“…Cells were cultured in buffered RPMI 1640 supplemented with 10% (v/v) heat inactivated human AB serum (lot 2054; Gmini Bio-Products Inc, Calabasas, CA, USA) at 37°C with 5% CO 2 and 100% humidity as previously described21 for six days in the presence or absence of HCV proteins at a concentration of 1 μg/ml. Four purified recombinant HCV proteins were used (Microgen, Munich, Germany): NS3, NS4, NS5, and core.…”

Acute exacerbation during interferon alfa treatment of chronic hepatitis B: frequency and relation to serum ?-2 microglobulin levels

“…12,13,16 In contrast, during the reactivation episodes, serum HBsAg concentrations usually remain unchanged, and the proliferative response of T lymphocytes to HBV envelope antigens remains weak and undetectable. 5 However, in this study, we detected a preceding HBV-DNA rise in only 3 of 11 patients (1 of whom was HBeAg ϩve), and peak values were not too striking (Ͻ3 times basal HBV-DNA value).…”

“…[1][2][3]13 This is marked by increased hepatocyte destruction as the result of increased hepatocyte HLA class I antigen expression followed by an attack of cytotoxic T cells and is characterized by a sometimes striking increase in serum transaminase levels. [14][15][16] Previous studies showed that serum 2 -MG levels may be elevated by IFN treatment and the degree of the increase was associated with the magnitude of HLA class I antigen expression on hepatocytes. [7][8][9] In this study, serum 2 -MG levels were higher in responders, before as well as during treatment, in comparison with nonresponders.…”

New Animal Models of Hepatitis B and C

“…Strong evidence exists that the pathogenesis of HBV infection is immune mediated. For example, liver and peripheral blood lymphocytes demonstrate proliferative and cytotoxic activities against HBV antigens (Feitelson 1996;Ferrari et al 1987;Marinos et al 1995). In addition, HBVinfected patients under immunosuppressive therapy often have widespread virus gene expression in the liver and high levels of virus in the serum without liver disease; however, they often develop severe liver disease when immunosuppressive therapy is terminated and antiviral immune responses reappear (Bianchi and Gudat 1979).…”