Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis

• Published in: The Journal of experimental medicine Vol. 199; no. 7; pp. 971 - 979
• Main Authors: Viglietta, Vissia, Baecher-Allan, Clare, Weiner, Howard L, Hafler, David A
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 05-04-2004
• Subjects: Adult; Animals; Autoimmune Diseases - immunology; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; Female; Humans; Immunization; In Vitro Techniques; L-Selectin - metabolism; Mice; Middle Aged; Multiple Sclerosis - immunology; Receptors, Antigen, T-Cell - metabolism; Receptors, Interleukin-2 - metabolism; Self Tolerance; Signal Transduction; T-Lymphocyte Subsets - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20031579

CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T cells expressing high levels of CD25 are suppressive in vitro and mimic the activity of murine CD4+CD25+ regulatory T cells. Multiple sclerosis (MS) is an inflammatory disease thought to be mediated by T cells recognizing myelin protein peptides. We hypothesized that altered functions of CD4+CD25hi regulatory T cells play a role in the breakdown of immunologic self-tolerance in patients with MS. Here, we report a significant decrease in the effector function of CD4+CD25hi regulatory T cells from peripheral blood of patients with MS as compared with healthy donors. Differences were also apparent in single cell cloning experiments in which the cloning frequency of CD4+CD25hi T cells was significantly reduced in patients as compared with normal controls. These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS.