Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Regulatory T Cells Directly Suppress B Cells in Systemic Lupus Erythematosus
Iikuni, Noriko, Lourenco, Elaine V., Hahn, B. H., La Cava, Antonio
In systemic lupus erythematosus (SLE), adaptive CD4+CD25+Foxp3+ cells (Tregs) suppress T helper (Th) cells that help autoantibody (autoAb)-producing B cells. It is not known whether naturally occurring Tregs can directly suppress B cells in SLE without an intermediate suppression of Th cells. This aspect is important for its implications in the natural course of SLE, because most if not all of the clinical and pathologic effects in SLE associate with a dysregulated production of autoAb.
Lupus Tregs were incubated with B cells in the absence of Th cells, and suppression of B cells was investigated.
Natural Tregs inhibited B-cell activity in vitro (P<0.005) and in vivo (P<0.04) in SLE, independently of age, through cell contact-mediated mechanisms that directly suppress autoAb-producing B cells, including those B cells that increase numerically during active disease in SLE patients such as CD19+CD27high (P<0.009) and CD19+CD27-IgD- (P<0.0007) B cells. Using blocking antibodies and cells infected with dominant negative receptors, we identified membrane-bound TGFb on Tregs and TGFb receptor II on B cells as key molecules for the direct suppressive activity of Tregs on B cells.
The dat indicate that one way by which natural Tregs attempt to limit humoral autoimmunity in SLE is by directly targeting autoAb-producing B cells.
To cite this abstract, please use the following information:
Iikuni, Noriko, Lourenco, Elaine V., Hahn, B. H., La Cava, Antonio; Regulatory T Cells Directly Suppress B Cells in Systemic Lupus Erythematosus [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1075