July 30, 2007 Autoimmune diseases such as multiple sclerosis and arthritis result from the body’s immune system attacking it’s own tissues or ‘self antigens’. Therefore, researchers have long desired to understand how a state of immune tolerance (the inability to mount an immune response against an antigen) may be forcibly induced as a therapeutic approach to treating autoimmune disease.
In a study appearing online on July 26 in advance of publication in the August print issue of the Journal of Clinical Investigation, Masato Tanaka and colleagues from RIKEN Research Center for Allergy and Immunology in Japan investigated the contribution of cells in the spleen known as macrophages to the establishment of immunological tolerance.
The authors generated transgenic mice in which macrophages in an area known as the marginal zone in the spleen were transiently deleted by the administration of diphtheria toxin (DT). In healthy mice, injected, dying cells are normally selectively engulfed and destroyed by immune cells known as dendritic cells, and as such the presence of cell-associated antigens does not trigger an immune response.
By contrast, in DT-treated mice that lacked macrophages in the marginal zone of the spleen, the ingestion and destruction of the dying cells by dendritic cells was irregular and the mice became susceptible to the development of a multiple sclerosis-like autoimmune response.
This is the first study demonstrating that macrophages in the marginal zone of the spleen regulate not only efficient clearance of dying cells, but also the selective engulfment of dying cells by dendritic cells, and that functional failure of these macrophages impairs the induction of tolerance to cell-associated antigens.
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