Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
B Cells Modify Regulatory T Cells in Healthy Individuals but Not in Patients with Systemic Lupus Erythematosus.
N. Lazarus, Mark, S. Kalsi, Hardeep, A. Isenberg, David, R. Ehrenstein, Michael
A number of publications have demonstrated that B cells can modify regulatory T cells (Treg) number indicating that B cells could contribute to the maintenance of tolerance via effects on Treg. B cell depletion therapy is currently used to treat some patients with systemic lupus erythematosus, but conflicting results have been obtained on the effects on Treg. We therefore investigated whether Treg are affected by removal of B cells in vitro and in vivo.
Treg were enumerated in healthy individuals and patients with lupus before and after rituximab therapy and correlated with B cell numbers. Intracellular cytokine staining for IL-2 and interferon gamma was performed in some assays. Peripheral blood mononuclear cells (PBMC) from healthy controls and lupus patients were cultured whole or following depletion of B cells by MACS LD beads and stimulated with anti-CD3/CD28. CD4, Foxp3 and CD25 expression assayed after 3 days using FACS.
In patients with SLE, Foxp3 expression was significantly increased compared to healthy controls (p<0.001). Both CD4+Foxp3+ and CD4Foxp3hi T cells were significantly increased compared to healthy individuals. CD4+Foxp3+ T cells did not produce any IL-2 or interferon gamma suggesting that these are not simply activated T cells. Following B cell depletion, the increased frequency of Treg compared to healthy controls remained unchanged during depletion and repopulation. There was a strong correlation between Treg numbers and the CD19:CD4 ratio in healthy individuals (r2 0.6059, p<0.005), but not in lupus patients. Treg numbers were significantly reduced in the PBMC of healthy individuals (p<0.001) but not lupus patients following removal of B cells in vitro.
B cells partly drive an increase in Treg numbers in vitro following activation in healthy individuals. However, this was not observed in PBMC from lupus patients suggesting that this control on Treg is defective. The notion that the increased frequency of Treg in lupus patients is driven by B cell independent mechanisms is supported by our observation that Foxp3 expression remains unchanged following B cell depletion therapy and that a strong correlation between Treg frequency and B:T cell ratio in healthy individuals is lost in patients with SLE.
To cite this abstract, please use the following information:
N. Lazarus, Mark, S. Kalsi, Hardeep, A. Isenberg, David, R. Ehrenstein, Michael; B Cells Modify Regulatory T Cells in Healthy Individuals but Not in Patients with Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :738