title: A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8(+) T cell responses to rabies virus.
abstract: Inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. Here, we analyzed the effect of GM-CSF on a RABV-vaccine vector co-expressing HIV-1 Gag. To this end, we immunized mice with RABV expressing HIV-1 Gag and GM-CSF and analyzed the primary and recall CD8(+) T cell responses. We observed a statistically significant increase in antigen presenting cells (APCs) in the spleen and draining lymph nodes in response to GM-CSF. Despite the increase in APCs, the primary and memory anti HIV-1 CD8(+) T cell response was significantly lower. This was partly likely due to lower levels of proliferation in the spleen. Animals treated with GM-CSF neutralizing antibodies restored the CD8(+) T cell response. These data define a role of GM-CSF expression, in the regulation of the CD8(+) T cell immune responses against RABV and has implications in the use of GM-CSF as a molecular adjuvant in vaccine development.
authors.affiliation: Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Celestine N
authors.initials: CN
authors.lastname: Wanjalla
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Goldstein
authors.forename: Christoph
authors.initials: C
authors.lastname: Wirblich
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011818:Rabies / Q000276:immunology* / Q000821:virology; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D054301:gag Gene Products, Human Immunodeficiency Virus; D016178:Granulocyte-Macrophage Colony-Stimulating Factor