Immunization with high-dose warmth shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg) frequency and suppressive function. of CD4+ T cells that highly express IL-2R chain RGS3 (CD25), and their differentiation and function are controlled by the forkhead/winged helix transcription factor (Foxp3) . The activation and suppressive function of Tregs require TCR signaling and activation by TGF- and IL-2 . Tregs suppress the activation, proliferation, di?erentiation, and e?ector functions of many cell types, including CD4+ and CD8+ T cells, and play a major role in maintaining immune homeostasis and immune tolerance to self-Ag, order Cisplatin as well as to pathogens and tumors [3C5]. Suppression of standard T cells by Tregs entails immunosuppressive soluble factors (e.g., TGF- and IL-10) and cell-cell contact . Due to their potent immune regulatory phenotypes, manipulation of Treg cell activity provides huge therapeutic potential to restrain immune hyperactivation in autoimmunity, inflammation, and allograft rejection [2,7,8]. The immunomodulatory role of Tregs in hepatitis B computer virus (HBV) an infection with different disease levels has been extensively analyzed. Higher frequencies of Tregs are observed in chronic hepatitis B (CHB). They suppress viral-specific T cell reactions and play a key part in maintenance of immune tolerance to HBV and viral persistence [4,9]. On the other hand, as hepatic T lymphocytes- and NK cells-mediated swelling is involved in the pathogenesis of HBV-induced chronic liver diseases [10C12], Tregs may play a key part in intrahepatic immune rules. Treg frequency offers been shown to be inversely correlated with immune-mediated liver injury and pathogenesis of HBV-associated fibrosis progression and liver failure [13,14], and the decrease of HBcAg peptide-specific Treg cells may partially account for acute exacerbation of CHB [15,16], though the exact mechanisms of Treg function await further investigation. Furthermore, a study performed inside a mouse model of acute HBV illness demonstrates that Tregs restrain immune-mediated liver damage by suppressing effector T cells via inhibition of cytokine production and cytotoxicity at the cost of delaying computer virus clearance . Concanavalin A (Con A)-induced liver damage in the mouse is definitely a well-characterized order Cisplatin model of T cell-dependent experimental liver injury , and has been used to investigate the immune-mediated pathology of autoimmune hepatitis and viral hepatitis. Intravenous injection of mice with Con A activates T lymphocytes and induces secretion of Th1 cytokines, and prospects to symptoms of acute hepatitis, including lymphocyte infiltration in the liver, hepatocyte necrosis and elevated ALT levels, which resemble the pathophysiology of T cell-mediated hepatic injury and order Cisplatin liver diseases [19C21]. Heat shock protein gp96, the endoplasmic reticulum form of Hsp90, takes on an important part in modulating innate and adaptive immunity [22,23]. Owing to its unique immunogenicity, clinical tests have been initiated using autologous gp96-peptide complexes for treatment of cancers . In our earlier study, we used titrated doses of gp96 (0, 0.5, 5, 10, 20, 50, 100 and 200 g/mice) for immunization and found that 10-20 g of gp96 elicited the highest CTL responses, but a dramatic decrease in CTL activity was observed when the immunization dose increased to 50-100 . We as well as others have further shown that activation of CTL at low dose of gp96 is definitely far more pronounced than Treg activation, however, high-dose gp96 immunization of mice significantly enhances Treg.