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.

Keywords: Diffuse large B cell lymphoma; Follicular helper T cell; Interleukin 10.