Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells.
Cimetidine (CIM), a histamine 2-receptor antagonist, is postulated to enhance immune responses owing to its inhibitory effects on suppressor T cells. In this report, we evaluated effects of cimetidine on the potency of antigen-specific immunity generated by DNA vaccine encoding hepatitis B surface antigen (HBsAg, pcD-S2). Our data demonstrate that CIM as adjuvant significantly increased HBsAg-specific cell-mediated and humoral immunities that were characterized by higher Ig2a/IgG1 ratio. In addition, CIM significantly promotes an elevated level of IL-4 and IFN-gamma in antigen-specific CD4(+) T cells and a robust antigen-specific cytotoxic response in the animals immunized with pcD-S2 plus CIM. Further, CIM induces pro-inflammatory cytokine expression such as the IL-12 and down-regulates anti-inflammatory cytokine expression such as IL-10 and TGF-beta, which may lead to an impairment of CD4(+)CD25(+) Treg cell-mediated suppression. Collectively these findings suggest that CIM enhances the immune responses of HBV DNA vaccine through the stimulation of pro-inflammatory and inhibition of anti-inflammatory cytokine expression patterns.
Wang
Junpeng
J
State Key Laboratories of Agro-biotechnology, College of Biological Science, China Agricultural University, Beijing 100094, China.
Su
Baowei
B
Ding
Zheng
Z
Du
Xiaogang
X
Wang
Bin
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
D000276:Adjuvants, Immunologic; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006635:Histamine H2 Antagonists; D019444:Vaccines, DNA; D018664:Interleukin-12; D015847:Interleukin-4; D002927:Cimetidine; D007371:Interferon-gamma