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Immunology. 2008 Jun;124(2):149-54. doi: 10.1111/j.1365-2567.2008.02821.x. Epub 2008 Apr 2.

T-cell regulation by CD46 and its relevance in multiple sclerosis.

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Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK.


CD46 is a complement regulatory molecule expressed on every cell type, except for erythrocytes. While initially described as a regulator of complement activity, it later became a 'magnet for pathogens', binding to several viruses and bacteria. More recently, an alternative role for such complement molecules has emerged: they do regulate T-cell immunity, affecting T-cell proliferation and differentiation. In particular, CD46 stimulation induces Tr1 cells, regulatory T cells characterized by massive production of interleukin-10 (IL-10), a potent anti-inflammatory cytokine. Hence, CD46 is likely to control inflammation. Indeed, data from CD46 transgenic mice highlight a role for CD46 in inflammation, with antagonist roles depending on the cytoplasmic tail being expressed. Furthermore, recent data have shown that CD46 is defective in multiple sclerosis, IL-10 production being severely impaired in these patients. This lack of IL-10 production probably participates in the inflammation observed in patients with multiple sclerosis. This review will summarize the data on CD46 and T cells, and how CD46 is likely involved in multiple sclerosis.

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