Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Exp Cell Res. 2020 Apr 1;389(1):111892. doi: 10.1016/j.yexcr.2020.111892. Epub 2020 Feb 5.
CXCR5 CD8 T cells, sometimes termed T follicular cytotoxic (Tfc) cells, are characterized by high proinflammatory cytokine and cytolytic molecule expression and low exhaustion and checkpoint molecule expression. Additionally, Tfc cells could promote B cell responses and support Ig release. It is yet unclear how Tfc cells could help B cells when they have the potential to mediate cytotoxicity at the same time. In this study, we found that Tfc cells expressed significantly higher levels of CD40L than non-Tfc CD8 T cells. Interestingly, Tfc cells from colorectal cancer (CRC) patients presented significantly higher CD40L than Tfc cells from healthy controls in a manner that was associated with CRC stage. Coincubation of Tfc cells and autologous B cells resulted in higher CD40L expression in a time-dependent manner. Interestingly, activated Tfc cells, when incubated with B cells, presented rapid downregulation of perforin and granzyme B. In general, greater than 50% of tumor-infiltrating Tfc cells expressed CD40L. In addition, the level of CD40L in tumor-infiltrating Tfc cells was higher in stage IV CRC patients than in stage II and stage III CRC patients. Interestingly, the levels of perforin and granzyme B expression by tumor-infiltrating Tfc cells were inversely correlated with the level of CD40L expression by tumor-infiltrating Tfc cells. Overall, we demonstrated that an inverse association existed between CD40L and cytotoxic molecule expression in Tfc cells from CRC patients.
CXCR5+CD8+T 细胞，有时也被称为滤泡辅助性细胞毒性 T（Tfc）细胞，其特征是高水平的促炎细胞因子和细胞毒性分子表达，以及低水平的衰竭和检查点分子表达。此外，Tfc 细胞可以促进 B 细胞反应并支持 Ig 释放。目前尚不清楚 Tfc 细胞在具有同时介导细胞毒性的潜力的情况下如何帮助 B 细胞。在这项研究中，我们发现 Tfc 细胞表达的 CD40L 水平明显高于非 Tfc CD8+T 细胞。有趣的是，CRC 患者的 Tfc 细胞表达的 CD40L 明显高于健康对照者，且与 CRC 分期相关。Tfc 细胞与自体 B 细胞共培养可导致 CD40L 表达呈时间依赖性增加。有趣的是，激活的 Tfc 细胞与 B 细胞孵育时，穿孔素和颗粒酶 B 的表达迅速下调。总体而言，大于 50%的肿瘤浸润性 Tfc 细胞表达 CD40L。此外，IV 期 CRC 患者肿瘤浸润性 Tfc 细胞中 CD40L 的水平高于 II 期和 III 期 CRC 患者。有趣的是，肿瘤浸润性 Tfc 细胞中穿孔素和颗粒酶 B 的表达水平与肿瘤浸润性 Tfc 细胞中 CD40L 的表达水平呈负相关。总体而言，我们证明了 CRC 患者 Tfc 细胞中 CD40L 与细胞毒性分子表达之间存在反比关系。
