CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer
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Weiwei Wang1, Xiangliang Yuan1, Hui Chen1, Guohua Xie1, Yanhui Ma1, Yingxia Zheng1, Yunlan Zhou1 and Lisong Shen1
1 Department of Clinical Laboratory, Xinhua Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Lisong Shen, email:
Keywords: gastric cancer, regulatory B cells, IL-10, TGF-β, regulatory T cells, immune escape
Received: January 30, 2015 Accepted: August 23, 2015 Published: September 10, 2015
Regulatory B cells (Bregs) play a critical role in inflammation and autoimmune disease. We characterized the role of Bregs in the progression of gastric cancer. We detected an increase in Bregs producing IL-10 both in peripheral blood mononuclear cells (PBMCs) and in gastric tumors. Multicolor flow cytometry analysis revealed that a subset of CD19+CD24hiCD38hi B cells produces IL-10. Functional studies indicated that increased Bregs do not inhibit the proliferation of CD3+T cells or CD4+ helper T cells (Th cells). However, Bregs do suppress the secretion of IFN-γ and TNF-α by CD4+Th cells. CD19+CD24hiCD38hiBregs were also found to correlate positively with CD4+FoxP3+ regulatory T cells (Tregs). Neutralization experiments showed that Bregs convert CD4+CD25- effector T cells to CD4+FoxP3+Tregs via TGF-β1. Collectively, these findings demonstrate that increased Bregs play a immunosuppressive role in gastric cancer by inhibiting T cells cytokines as well as conversion to Tregs. These results may provide new clues about the underlying mechanisms of immune escape in gastric cancer.
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