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.
TGF--Induced CD4Foxp3 Cells Suppress Lupus-Like Syndrome through Induction of Formation of Tolerogenic DC.
Zhou4, Xiaohui, Wang4, Julie, Horwitz2, David A., Fan3, Huimin, Zou1, Hejian, Liu3, Zhongmin, Zheng4, Song Guo
Regulatory T cells (Tregs) play vital roles in maintaining immune homeostasis and self tolerance. Recent studies revealed that dendritic cells (DCs) might be main target of Tregs and also induce immune tolerance. We have previously reported that adoptive transfer of TGF-b-induced Tregs (iTregs) prevents the appearance of lupus syndrome induced by injection of DBA/2 mouse splenocytes to (DBA/2 × C57BL/6) F1 mice, we here ask if interaction between iTregs and DCs contributes to disease control.
Materials and Methods:
DBA/2 naïve CD4+ cells were stimulated with anti-CD3/CD28 beads and IL-2 ± TGF-b (control or iTregs) for 5 days. 5×106 control or iTregs with 80×106 DBA/2 splenocytes were adoptively transferred to F1 mice. ALK-5 inhibitor and anti-IL-10R Ab were i.p injected twice a week for four weeks in some groups. On day 11 after transfer of control or iTregs, CD11c+ cells were selected from splenocytes in F1 mice and injected (1×106) with 80×106 DBA/2 splenocytes to F1 mice. Surface and intracellular staining included CD80, CD86, CD11c, IA-b, Foxp3, CD25, H-2Kd, H-2Kb. IgG and anti-DNA in sera was analyzed with ELISA and mice survival was monitored.
A single injection of 5×106 iTregs markedly prevented increased IgG production, decreased anti-dsDNA autoantibodies, suppressed proteinuria and prolonged survival of these mice. The treatment with anti-TGF-b or ALK5 inhibitor completely, with anti-IL10R partially blocked the suppressive capacity of iTreg following injection in vivo. Moreover, iTreg suppressed CD80 and CD86 expression by DCs in vitro and in vivo. Adoptive transfer of these DCs in F1 mice received iTregs but not control cells to GVHD model can significantly prevent the development of lupus symptoms. The protective effect of these DCs was dependent on TGF-b/TbR signal but not IL-10/IL-10R signal. Thus, the protective effect of iTreg is dependent on TGF-b and/or IL-10 and formation of tolerogenic DCs that have developed TGF-b- but not IL-442-dependent suppression on lupus.
iTregs may suppress lupus-like syndrome through induction of formation of tolerogenic DC with TGF-b dependence pathway. iTregs may have therapeutic potential in treating autoimmune diseases.
To cite this abstract, please use the following information:
Zhou, Xiaohui, Wang, Julie, Horwitz, David A., Fan, Huimin, Zou, Hejian, Liu, Zhongmin, et al; TGF--Induced CD4Foxp3 Cells Suppress Lupus-Like Syndrome through Induction of Formation of Tolerogenic DC. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :442