The Mathilda and Terence Kennedy Institute of Rheumatology Trust

Brian Maurice John Foxwell

Marc Feldmann

Fionula Mary Brennan

We describe (1) a method of enhancing antigen presentation, comprising the step of supplying to an antigen presenting cell such as a dendritic cell, or precursor cell, an inhibitor of Toll-related receptor (TRR) signalling and (2) a method of inhibiting antigen presentation, comprising the step of supplying to an antigen presenting cell such as a dendritic cell, or precursor cell, an enhancer of Toll-related receptor (TRR) signalling. The inhibitor of TRR signalling may be a dominant negative mutant of MyD88, for example MyD881pr.

Methods for enhancing antigen presentation

A method of identifying a compound with efficacy in the treatment of chronic inflammatory disease by testing the compound for an ability to selectively inhibit the ability of Tcells to induce pro-inflammatory cytokine release from a monocyte is disclosed. The method includes pre-incubatin Tcells with a compound to be tested, optionally resuspending the Tcells in the absence of the test compound, co-culturing the Tcells with monocytes, and assaying for the production of pro-inflammatory cytokines by the monocytes. The Tcells are produced by incubating a population of T cells with one or more cytokines or the Tcells are isolated from synovial tissue. The Tcells have not been contacted with an anti-CD3 antibody. The ability to selectively inhibit cytokine release indicates that the compound has efficacy in the treatment of chronic inflammatory disease.

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London, United Kingdom

Brian Maurice John Foxwell