Multiple Regulatory Cell Types Can't Keep Self-destructive Immune Cells Under Control

Multiple sclerosis (MS) is an autoimmune disease that occurs when cells of the immune system attack nerves in the brain. Although it is not clear exactly why this self destruction is able to occur, it has been shown that other immune cells that normally keep the destructive ones in check (known as regulatory T cells) are impaired in individuals with MS. Previous studies have focused on a regulatory T cell subset known as the CD4+CD25high regulatory T cell subset, but in a study which appeared online on November 9, in advance of publication in the December print issue of the Journal of Clinical Investigation, researchers from Harvard University, now show that IL-10 producing regulatory T cells (Tr1 cells) are also impaired in individuals with MS.



David Hafler and colleagues showed that T cells from patients with MS produced substantially less IL-10 when stimulated ex vivo with antibodies specific for CD3 and CD46 than T cells from healthy individuals. This inability to induce a Tr1 cell phenotype was associated with altered expression of CD46 cytoplasmic isoforms upon activation. This study shows that a second regulatory T cell population (the Tr1 cells) is impaired in individuals with MS and the authors speculate that, as for the CD4+CD25high regulatory T cell subset, this defect is likely to be observed in patients with other autoimmune diseases, such as rheumatoid arthritis.



TITLE: Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis



AUTHOR CONTACT:


David A. Hafler

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.



Anne L. Astier

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.






JCI table of contents: November 9, 2006



Contact: Karen Honey

Journal of Clinical Investigation