title: Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway.
abstract: Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5+CD4+T cells, in DLBCL. Data showed that compared to CXCR5-CD4+T cells, CXCR5+CD4+T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5+CD4+T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5-CD4+T cells, while the level of IL-10 secretion was significant elevated in the CXCR5+compartment compared to the CXCR5-compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5+CD4+T cell coculture compromised the CXCR5+CD4+T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5+compartment also contained significantly lower frequencies of cytotoxic CD4+T cells than the CXCR5-compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4+T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10.
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhanshan
authors.initials: Z
authors.lastname: Cha
authors.affiliation: Department of Endocrinology, Zhangqiu Municipal Hospital of Traditional Chinese Medicine, Zhangqiu, Shandong 250200, China.
authors.forename: Guangfang
authors.initials: G
authors.lastname: Qian
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zang
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Lishuang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jinqi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tu
authors.affiliation: Emergency Center, East Hospital, Shanghai 200120, China.
authors.forename: Haihan
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: qianbhl963@163.com.
authors.forename: Baohua
authors.initials: B
authors.lastname: Qian
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D054380:Receptors, CXCR5 / Q000276:immunology*; D015398:Signal Transduction; D000098546:Interleukin-21
chemical_list: C095085:CXCR5 protein, human; C508609:IL10 protein, human; D007378:Interleukins; D054380:Receptors, CXCR5; D016753:Interleukin-10; D000098546:Interleukin-21
keywords: Diffuse large B cell lymphoma; Follicular helper T cell; Interleukin 10