In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes.
The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ Tregs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded Tregs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.
Tang
Qizhi
Q
UCSF Diabetes Center, University of California San Francisco, 94143, USA.
Henriksen
Kammi J
KJ
Bi
Mingying
M
Finger
Erik B
EB
Szot
Greg
G
Ye
Jianqin
J
Masteller
Emma L
EL
McDevitt
Hugh
H
Bonyhadi
Mark
M
Bluestone
Jeffrey A
JA
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001324:Autoantigens; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2