Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway.

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.