Regulatory T cells use programmed death 1 ligands to directly suppress autoreactive B cells in vivo.
The mechanisms by which regulatory T cells (T(regs)) suppress autoantibody production are unclear. Here we have addressed this question using transgenic mice expressing model antigens in the kidney. We report that T(regs) were essential and sufficient to suppress autoreactive B cells in an antigen-specific manner and to prevent them from producing autoantibodies. Most of this suppression was mediated through the inhibitory cell-surface-molecule programmed death-1 (PD-1). Suppression required PD-1 expression on autoreactive B cells and expression of the two PD-1 ligands on T(regs). PD-1 ligation inhibited activation of autoreactive B cells, suppressed their proliferation, and induced their apoptosis. Intermediate PD-1(+) cells, such as T helper cells, were dispensable for suppression. These findings demonstrate in vivo that T(regs) use PD-1 ligands to directly suppress autoreactive B cells, and they identify a previously undescribed peripheral B-cell tolerance mechanism against tissue autoantigens.
Institutes of Molecular Medicine and Experimental Immunology, Rheinische Friedrich-Wilhelms-Universität, 53105 Bonn, Germany.
Janine
J
Gotot
Catherine
C
Gottschalk
Sonny
S
Leopold
Percy A
PA
Knolle
Hideo
H
Yagita
Christian
C
Kurts
Isis
I
Ludwig-Portugall
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008024:Ligands; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D017931:DNA Primers; D008024:Ligands; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor