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Influence of T‐helper cell subsets and crossregulation in hepatitis B virus infection
Author(s) -
Milich D. R.
Publication year - 1997
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.1997.tb00180.x
Subject(s) - virology , hepatitis b virus , virus , immunology , biology , t helper cell , hepatitis b , t cell , medicine , immune system
Summary. Serological and biochemical studies indicate that acute HBV infection is resolved in the context of an efficient cell‐mediated immune (CMI) response, whereas, chronic infection is characterized by weak to undetectable CMI responses and relatively efficient humoral immunity. Because humoral immunity and CMI are regulated by different TH subsets, factors which influence the induction of TH 1 vs TH 2 cells specific for the HBV nucleocapsid antigens (HBcAg, HBeAg) were examined in a murine model system. The factors which affected the HBc/HBeAg‐specific TH 1 /TH 2 ‐cell balance included: (1) the structure of the antigen (i.e. HBcAg vs HBeAg); (2) the host MHC and T‐cell site recognized; (3) crossregulation between TH 1 and TH 2 cells; (4) T‐cell tolerance, which is more complete in TH 1 than in TH 2 cells; (5) secreted HBeAg, which preferentially depletes TH 1 cells; (6) the HBV‐specific subset response could be skewed towards either TH 1 or TH 2 predominance by cytokine treatment in vivo. The results suggest that the balance between TH 1 and TH 2 cells specific for the HBc/HBeAgs may be relevant in acute and chronic HBV infections. Importantly, HBeAg‐specific TH 2 cells preferentially evade tolerance induction as compared to their TH 1 ‐cell counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic HBV infection and preferentially depletes TH 1 cells in the circulation, the predominance of HBeAg‐specific TH 2 cells may influence the initiation or maintenance of the chronic carrier state. In this case, cytokine therapy designed to shift a TH 2 ‐like response toward TH 1 predominance (i.e. IL‐12) may be beneficial in the treatment of chronic HBV infection.