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The Effect of Gene Gun‐delivered pGM‐CSF on the Immunopathology of the Vaccinated Skin
Author(s) -
Matthews K.,
Rhind S. M.,
Gossner A. G.,
Dalziel R. G.,
Hopkins J.
Publication year - 2007
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2007.01902.x
Subject(s) - gene gun , immune system , immunology , infiltration (hvac) , cytokine , tumor necrosis factor alpha , immunopathology , biology , granulocyte macrophage colony stimulating factor , epidermis (zoology) , gene expression , pathology , gene , medicine , immunization , dna vaccination , biochemistry , physics , anatomy , thermodynamics
The aim of this study was to investigate the skin immunopathology of gene gun‐delivered plasmid‐encoded granulocyte‐macrophage colony‐stimulating factor (pGM‐CSF) and hence explore the possible mechanisms of its adjuvant activity. Using sheep as the experimental model, expressible pGM‐CSF was administered to the epidermis and the dermal/epidermal junction and its effects on the skin were assessed by histopathology, immunohistology and quantitative RT‐PCR for a range of pro‐inflammatory and immune response‐polarizing cytokines. Both functional and non‐functional plasmids caused an acute inflammatory response with the infiltration of neutrophils and micro‐abscess formation; however, the response to pGM‐CSF was more severe and was also associated with the accumulation of eosinophils, immature (CD1b − /CD172a − ) dendritic cells and B cells. In terms of cytokine expression, an early TNF‐ α response was stimulated by gene gun delivery of plasmid‐associated gold beads, which coincided with an immediate infiltration of neutrophils. However, only pGM‐CSF triggered the short‐lived expression of GM‐CSF (peaking at 4 h) and significant long‐term increases in both TNF‐ α and IL‐1 β . pGM‐CSF did not affect the expression of the immune response‐polarizing cytokines, IL‐10 and IL‐12.