TY - JOUR
T1 - Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B
T2 - A major factor in activation of the host immune response to the hepatitis B virus
AU - Marinos, George
AU - Torre, Francesco
AU - Chokshi, Shilpa
AU - Hussain, Munther
AU - Clarke, Berwin E.
AU - Rowlands, David J.
AU - Eddleston, Adrian L.W.F.
AU - Naoumov, Nikolai V.
AU - Williams, Roger
PY - 1995/10
Y1 - 1995/10
N2 - 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 a-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 a-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.
AB - 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 a-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 a-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.
UR - http://www.scopus.com/inward/record.url?scp=0029147455&partnerID=8YFLogxK
U2 - 10.1016/0270-9139(95)90607-X
DO - 10.1016/0270-9139(95)90607-X
M3 - Article
C2 - 7557849
AN - SCOPUS:0029147455
SN - 0270-9139
VL - 22
SP - 1040
EP - 1049
JO - Hepatology
JF - Hepatology
IS - 4 PART 1
ER -
