Dendritic cells in autoimmune disease

There is a considerable body of evidence implicating dendritic cells in the pathology of autoimmune disease. Their number is elevated both in the serum and synovial fluid of patients with rheumatoid arthritis. Also, patients with multiple sclerosis have raised levels of circulating dendritic cells secreting proinflammatory cytokines. In diabetes, dendritic cells from people at high risk of the disease expressed low levels of co-stimulatory molecules affecting T cell responses.

Dendritic cells present antigen most effectively to naïve T cells. When dendritic cells are matured in the presence of proinflammatory cytokines, they are able to stimulate a Thrtype response through the release of IL-12. If inflammatory conditions do not prevail, dendritic cells are able to tolerise T cells or prime Th2-type responses. In autoimmune disease the balance between Thj and Th2 cells and between effector and regulatory T cells may influence disease progression.

In addition to presentation, processing of antigen by dendritic cells may be influenced by cytokines. As a result, antigenic determinants that are usually hidden (cryptic) may be presented to T cells rather than major antigenic determinants. This type of epitope spreading is seen in autoimmune diseases.

Murine dendritic cells were shown to present to T cells the dominant, not the cryptic, antigenic determinant of hen egg lysozyme. However, when the dendritic cells were treated with IL-6, the responding T cells preferentially recognised the cryptic determinants.

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