T-cell regulation by CD46 and its relevance in multiple sclerosis.
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.
Astier
Anne L
AL
Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK. a.astier@ed.ac.uk
D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051916:Membrane Cofactor Protein / Q000276:immunology*; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051916:Membrane Cofactor Protein; D016753:Interleukin-10; D003165:Complement System Proteins