Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis.
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.
Viglietta
Vissia
V
Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Baecher-Allan
Clare
C
Weiner
Howard L
HL
Hafler
David A
DA
D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D017634:Self Tolerance; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019041:L-Selectin