|
|
|
(Journal Article): TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes.
Belghith M, Bluestone JA, Barriot S, Megret J, Bach JF, Chatenoud L (INSERM U580, IRNEM, Hopital Necker, 161 Rue de Sevres, 75015 Paris, France.)
IN:
Nat Med
2003; 9(9):1202-1208
Impact Factor(s) of Nat Med: 28.878 (2005), 31.223 (2004), 30.55 (2003), 28.74 (2002), 27.906 (2001)
Fulltext:
HTML
PDF
ABSTRACT: CD3-specific antibodies have the unique capacity to restore self-tolerance in established autoimmunity. They induce long-term remission of overt diabetes in nonobese diabetic (NOD) mice and in human type I diabetes. The underlying mechanisms had been unclear until now. Here we report that treatment with CD3epsilon-specific antibodies induces transferable T-cell-mediated tolerance involving CD4+CD25+ cells. However, these CD4+CD25+ T cells are distinct from naturally occurring regulatory T cells that control physiological autoreactivity. CD3-specific antibody treatment induced remission in NOD Cd28-/- mice that were devoid of such regulatory cells. Remission of diabetes was abrogated by coadministration of a neutralizing transforming growth factor (TGF)-beta-specific antibody. The central role of TGF-beta was further suggested by its increased, long-lasting production by CD4+ T cells from tolerant mice. These data explain the intriguing tolerogenic effect of CD3-specific antibodies and position them as the first clinically applicable pharmacological stimulant of TGF-beta-producing regulatory CD4+ T cells.
TYPE OF PUBLICATION: Original article
Articles citing this article:
|
|
|
