Failure of carcinogen-altered dendritic cells to initiate T cell proliferation is associated with reduced IL-1 beta secretion.
The activation of T cells through presentation of antigen by dendritic cells (DC) relies on many factors, including the correct balance of cytokines in the immediate microenvironment. Antigen presentation by DC migrating from carcinogen-treated skin is impaired as evidenced by the failure of antigen-pulsed DC to initiate specific T cell proliferation. To elucidate mechanism(s) of DC dysfunction, DC migrating from carcinogen-treated skin were collected, pulsed with OVA, and cultured with antigen-specific autologous lymphocytes. Supernatants were assayed for the costimulatory cytokine IL-1 beta which influences the outcome of DC:T cell interactions. The dendritic cells migrating from carcinogen-treated skin that failed to induce T cell proliferation were unable to produce IL-1 beta. This may account for the abrogation of DC function following exposure to chemical carcinogens and provides an explanation for the inability of DC to induce a protective immune response to carcinogen-induced tumours.
Ragg
S J
SJ
Division of Pathology, University of Tasmania, Hobart, Australia.
Woods
G M
GM
Egan
P J
PJ
Dandie
G W
GW
Muller
H K
HK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D008196:Lymph / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D012756:Sheep / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D007375:Interleukin-1; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate