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Impact of cAMP on the T‐cell response to type II collagen
Author(s) -
Ozegbe Patricia,
Foey Andrew D.,
Ahmed Salman,
Williams Richard O.
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01768.x
Subject(s) - rolipram , cholera toxin , forskolin , type ii collagen , context (archaeology) , t cell , endocrinology , arthritis , immunology , medicine , prostaglandin e2 , interferon gamma , chemistry , biology , phosphodiesterase , cytokine , immune system , receptor , enzyme , biochemistry , paleontology
Summary There is considerable interest in the possible use of cAMP‐elevating agents in the treatment of autoimmune diseases such as rheumatoid arthritis. The objective of this study was to evaluate the impact of different cAMP‐elevating agents on the T‐cell response to type II collagen within the context of collagen‐induced arthritis, a murine model of rheumatoid arthritis. Spleen cells or lymph node cells from type‐II‐collagen‐immunized DBA/1 mice were cultured in the presence of type II collagen plus one of five different cAMP‐elevating agents: rolipram, forskolin, prostaglandin E 2 , 8‐bromo‐cAMP, or cholera toxin. Levels of interferon‐γ (IFN‐γ), interleukin‐4 (IL‐4) and IL‐5 were measured in culture supernatants by enzyme‐linked immunosorbent assay. All of the cAMP‐elevating agents tested were found to profoundly suppress IFN‐γ production in a dose‐dependent manner. IL‐4 and IL‐5 production was slightly up‐regulated at low concentrations of the cAMP‐elevating agents and was modestly suppressed at the highest concentrations of cAMP‐elevating agents. Experiments were then carried out to determine whether T cells were directly affected by cAMP‐elevating agents or whether the immunomodulatory effects were mediated via antigen‐presenting cells. Pulsing T cells alone for a brief period with cholera toxin produced an almost identical effect to pulsing antigen‐presenting cells alone, i.e. down‐regulation of proliferation, down‐regulation of IFN‐γ production with little effect on IL‐5 production. It was concluded that cAMP‐elevating agents suppressed T helper type 1 responses to type II collagen to a greater extent than T helper type 2 responses. The cAMP‐elevating agents could directly influence the activity of T cells but, in addition, influenced the ability of antigen‐presenting cells to support T helper type 1 responses.