Published 5 April 2004. doi:10.1084/jem.20031579
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 7, 971-979
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Vissia Viglietta,
Clare Baecher-Allan,
Howard L. Weiner, and
David A. Hafler
Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Address correspondence to David A. Hafler, Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, MA 02115. Phone: (617) 525-5330; Fax: (617) 525-5333; email: dhafler{at}rics.bwh.harvard.edu
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.
Key Words: tolerance autoreactive T cells autoimmune disease L-selectin
V. Viglietta and C. Baecher-Allan contributed equally to this work.
Abbreviations used in this paper: CNS, central nervous system; MBP, myelin basic protein; MS, multiple sclerosis; RR, relapsing/remitting.

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