A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8(+) T cell responses to rabies virus

Virology. 2012 May 10;426(2):120-33. doi: 10.1016/j.virol.2012.01.025. Epub 2012 Feb 16.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / genetics
  • Animals
  • Antigen-Presenting Cells / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Rabies / immunology*
  • Rabies / virology
  • Rabies virus / genetics
  • Rabies virus / immunology*
  • Spleen / immunology
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Adjuvants, Immunologic
  • gag Gene Products, Human Immunodeficiency Virus
  • Granulocyte-Macrophage Colony-Stimulating Factor