BACKGROUND: @entity70396 (LF), a novel analogue of @entity5101 ( @entity5252 ), inhibits maturation of dendritic cells (DC). Anti-CD45RB is a monoclonal antibody (mAb) that blocks activation of T-helper (Th) 1 cells and generates T-regulatory cells. This study addressed whether these two reagents act synergistically to inducing tolerance, and investigated associated cellular mechanisms. METHODS: BALB/c recipients were treated by a short course of mAb alone, LF alone, or the combination of both agents. @entity19 that accepted a C57BL/6 cardiac allograft for more than 100 days were considered tolerant. Splenic DC were purified using positive selection for @entity11805 . Bone marrow DC were generated by culture with @entity58 . Surface marker expression was determined by fluorescence-activated cell sorter analysis. DC function was assessed by the ability to stimulate or inhibit T cells in vitro. RESULTS: Although monotherapy with LF or mAb failed to induce tolerance, combination therapy resulted in long-lasting acceptance of allogeneic hearts (>200 days) and secondary donor skin grafts (>100 days). DC from tolerant recipients possessed lower major histocompatibility complex class II and @entity14636 expression, and were poorer co-stimulators for T-cell proliferation than control DC. Furthermore, DC from tolerant @entity19 induced Th2 differentiation, suppressed overall T-cell proliferation, and were poor presenters of T cells specific for antigen to pigeon cytochrome c 81-104. CONCLUSIONS: The combination of LF and anti-CD45RB mAb induced stable tolerance. The synergy of these two approaches appears to be mediated through formation of tolerogenic DC and T-regulatory cells.

Synergistic tolerance induced by XXXX and anti-CD45RB monoclonal antibody through suppressive dendritic cells.

@entity70396 :: ('MESH:C434185', 'Chemical') :: ['LF 15-0195'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity14636 :: ('21939(Tax:10090)', 'Gene') :: ['CD40'] @entity5101 :: ('MESH:C037258', 'Chemical') :: ['15-deoxyspergualin'] @entity5252 :: ('CHEBI:62094', 'Chemical') :: ['DSG'] @entity58 :: ('16189(Tax:10090)', 'Gene') :: ['interleukin-4 and granulocyte-macrophage colony-stimulating factor'] @entity11805 :: ('16411(Tax:10090)', 'Gene') :: ['CD11c']
@entity70396 :: (MESH:C434185,Chemical) :: ['LF15-0195']
