Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8531054 | International Immunopharmacology | 2018 | 8 Pages |
Abstract
CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells possess critical roles in suppressing the germinal center reaction, B cell activation, and follicular helper T cell (Tfh) cytokine secretion. Since diffuse large B cell lymphoma (DLBCL) can arise from B cells undergoing germinal center reaction and/or differentiation, we hypothesized that Tfr cells might be involved in DLBCL. In the present study, we recruited thirty-five DLBCL patients and twenty-five healthy controls. Data showed that DLBCL patients presented an enrichment of circulating CD4+CXCR5+Foxp3+ Tfr cells compared to controls. In the primary tumor isolated from enlarged lymph nodes, Tfr cells made up of roughly 3% to 16% of infiltrating T cells. Higher levels of tumor-infiltrating Tfr cells were observed in patients with less advanced DLBCL stages, and in patients that stayed in remission 24â¯months after the initial R-CHOP treatment. High BCL6 and high FOXP3 expression was observed in Tfr cells ex vivo. After anti-CD3/CD28 and IL-2 stimulation, the Tfr cells more closely resembled Treg cells and presented high IL10 and TGFB1 expression. CD4+CD25+CXCR5+ Tfr cells and CD4+CD25+CXCR5â non-Tfr Treg cells could suppress CD4+CD25â Tconv cell and CD8+ T cell proliferation with similar capacity. However, Tfr cells were less capable of suppressing IFNG expression than Treg cells, and although both cell types supported CD19+ tumor cell proliferation, Tfr cells were less supportive than the non-Tfr Treg cells. Overall, this study suggested that Tfr cells were involved in intratumoral immunity, were likely beneficial to DLBCL patients, and were functionally distinctive from non-Tfr Treg cells. The distribution pattern and the prognostic value of Tfr cells in DLBCL should be examined in further studies.
Related Topics
Life Sciences
Immunology and Microbiology
Immunology
Authors
Zhanshan Cha, Haihui Gu, Yan Zang, Zi Wang, Jinqi Li, Weihua Huang, Aihua Qin, Lishuang Zhu, Xiaohua Tu, Ning Cheng, Haihan Song, Baohua Qian,