title: Macrophage colony-stimulating factor can modulate immune responses and attract dendritic cells in vivo.
abstract: Studies have indicated that professional APCs in the periphery, such as dendritic cells and macrophages, play an important role in initiating DNA vaccine-specific immune responses. To engineer the immune response induced by DNA vaccines in vivo we investigated the modulatory effects of codelivering growth factor genes for the hematopoietic APCs along with DNA vaccines. Specifically, we examined the effects on the antigen-specific immune responses following the codelivery of the gene expression cassettes for M-CSF, G-CSF, and GM-CSF along with HIV-1 DNA immunogen constructs. We observed that coimmunization with GM-CSF increased the antibody response and resulted in a significant enhancement of lymphoproliferative response. Furthermore, among all coinjection combinations, we found that M-CSF coinjections resulted in a high level of CTL enhancement. This enhancement of CTL responses observed from the coinjection with M-CSF was CD8+ T cell dependent and was associated with the presence of CD11c+ cells at the site of injection and with the antigen-specific induction of the beta-chemokine MIP-1beta, suggesting a role for this chemokine in CTL induction. These results suggest that hematopoietic growth factors should be further studied as potential adjuvants for in vivo modulators of immune responses.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: J S
authors.initials: JS
authors.lastname: Yang
authors.forename: D J
authors.initials: DJ
authors.lastname: Lee
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: L K
authors.initials: LK
authors.lastname: Nottingham
authors.forename: L
authors.initials: L
authors.lastname: Morrison
authors.forename: A
authors.initials: A
authors.lastname: Tsai
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.forename: K
authors.initials: K
authors.lastname: Dang
authors.forename: T
authors.initials: T
authors.lastname: Dentchev
authors.forename: M G
authors.initials: MG
authors.lastname: Agadjanyan
authors.forename: J I
authors.initials: JI
authors.lastname: Sin
authors.forename: A A
authors.initials: AA
authors.lastname: Chalian
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines / Q000494:pharmacology; D019742:Chemokines, CC / Q000096:biosynthesis; D003587:Cytomegalovirus / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000473:pathology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D019742:Chemokines, CC; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor