Aspirin modified dendritic cells are potent inducers of allo-specific regulatory T-cells.
Salicylic acid (aspirin) is a widely used pharmacological agent with immunodmodulatory properties. Dendritic cells are key regulators of the immune response, and are capable of inducing hyporesponsiveness and regulatory activity in CD4+ T-cells. We have demonstrated that aspirin-treated dendritic cells are effective at antigen processing and presentation, and possess a unique potency for inducing regulatory activity in responder T-cells. Unlike immature dendritic cells, aspirin DCs are resistant to the effects of maturational stimuli, as determined by low levels of CD40, CD80, CD83 and CD86 expression. Aspirin DCs were demonstrated to express high levels of the co-inhibitor of T-cell activation ILT-3. Aspirin DCs themselves produce less IL-10 and more IL-12 than immature DCs, but no specific cytokine is necessary for their tolerogenic capacity. When naïve CD4+ T-cells are exposed to aspirin DCs they produce significant levels of IFNgamma but these same T-cells are hypo-proliferative. Aspirin-treated DCs demonstrate the characteristics of a potential immunotherapy for controlling unwanted immune-responses such as the indirect pathway of allo-recognition that drives chronic allograft rejection.
Buckland
Matthew
M
Immunoregulation Laboratories, Department of Nephrology and Transplantation, King's College London School of Medicine at Guy's, King's College and St. Thomas' Hospitals, London, SE1 9RT, UK. matthew.buckland@kcl.ac.uk <matthew.buckland@kcl.ac.uk>
Jago
Charlotte
C
Fazekesova
Henrieta
H
George
Andrew
A
Lechler
Robert
R
Lombardi
Giovanna
G
D015703:Antigens, CD / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; D015848:Interleukin-5; D007519:Isoantigens; C107907:LILRB4 protein, human; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D001241:Aspirin