Activation of tonsil dendritic cells with immuno-adjuvants.
BACKGROUND
Dendritic cells (DC) play the key role in directing antigen-specific immune responses and manipulating their function may be a useful tool for immunotherapy. The balance between immune stimulation and tolerance is particularly important at mucosal interfaces, where discrimination between dangerous pathogens and innocuous antigens takes place. In humans, although much is known about the responses of monocyte derived DC, relatively little is known about effect of immuno-stimulatory adjuvants on DC found in tonsil.


RESULTS
To examine this, tonsil DC were isolated and cultured with potent DC activators; IFNgamma, anti-CD40 antibody, LPS and Poly I:C either singly or in combination. To measure maturation and activation, DC were examined for changes in the expression of HLA-DR, HLA- class I, CD83, CD40, CD80 and CD86 and the release of IL12p70. The DC isolated from tonsil were a mixed population containing both myeloid and plasmacytoid DC, but all showed similar responses. Tonsil DC released IL12p70 upon stimulation with IFNgamma , anti-CD40 antibody, and LPS, but unlike monocyte-derived DC, they did not increase the expression of cell surface activation molecules above those induced by culture alone. Poly I:C, a potent stimulator of laboratory generated DC inhibited the activation of tonsil DC by other adjuvants.


CONCLUSIONS
As the response of this mixed population of DC does not mirror that of DC generated in vitro, this may have implications for other tissue residing DC and might be an important consideration for immunotherapy.
Polak
Marta E
ME
Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth, UK. marta.polak@gmail.com
Borthwick
Nicola J
NJ
Gabriel
Francis G
FG
Jager
Martine J
MJ
Cree
Ian A
IA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000145:classification / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011070:Poly I-C