title: Interleukin-21 inhibits humoral response to an HIV DNA vaccine by enhancing Bcl-6 and Pax-5 expression.
abstract: Interleukin-21 (IL-21) is a T-cell-derived cytokine that modulates T-cell, B-cell, and natural killer cell responses. It is not known if it could be used as an adjuvant for HIV DNA vaccination. In our study, we investigated if a DNA construct expressing IL-21 (designated as pVAX-IL-21) as a molecule adjuvant could enhance antigen-specific immune responses to an HIV DNA vaccine (pGX-EnvC). We found that a higher level of antigen-specific cytotoxic responses was induced in BALB/C mice immunized with pGX-EnvC with the pVAX-IL-21 via electroporation. The increased response was associated with higher expression of IFN-γ in CD8⁺ T cells. In contrast, the administration of pVAX-IL-21 inhibited the antibody responses to HIV induced by the pGX-EnvC. The plasma cell inhibitory transcription factors B-cell lymphoma 6 protein (Bcl-6) and Pax-5 were increased in B cells from mice that had been immunized by HIV DNA vaccine plus pVAX-IL-21, suggesting that the expressed IL-21 may inhibit the differentiation from B cells to plasma cells. These results indicate that IL-21 could enhance CD8⁺ T-cell immunity, but inhibit humoral responses during HIV DNA vaccination.
authors.affiliation: State Key Laboratories of Agro-biotechnology, College of Biological Science, China Agricultural University, Beijing, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Feng
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.forename: Xuan
authors.initials: X
authors.lastname: Chen
authors.forename: Chenliang
authors.initials: C
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007378:Interleukins / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D051757:PAX5 Transcription Factor / Q000037:antagonists & inhibitors*; D051560:Proto-Oncogene Proteins c-bcl-6; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D016915:AIDS Vaccines; C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D015483:HIV Antibodies; D007155:Immunologic Factors; D007378:Interleukins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D019444:Vaccines, DNA; D000098546:Interleukin-21