Altered frequency of CD8+CD11c+ T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer
Altered frequency of CD8+CD11c+ T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer
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DOI：
10.1002/jcp.27856
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Babaloo, Zohreh
中科院分区：
文献类型：
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作者：
Rostamzadeh, Davood;Haghshenas, Mohammad Reza;Babaloo, Zohreh
CD 11 c是2-整联蛋白家族的成员，通常用于定义髓样树突状细胞（DC）。最近的报道将表达CD 11 c的CD 8（+）T细胞鉴定为CD 8（+）调节性T细胞（Treg）的新亚群。有证据表明，CD 11 c（+）CD 8（+）T细胞可以在不同条件下发挥其效应或调节功能。到目前为止，还没有研究涉及癌症中CD 11 c（+）T细胞的频率。在免疫检查点受体、程序性细胞死亡蛋白1（PD-1）和T淋巴细胞相关抗原4（CTLA-4）以及叉头盒P3（Foxp 3）在小鼠淋巴器官中的表达方面存在有限的证据。在此，我们评估了来自三组雄性BALB/c小鼠的不同组织中的CD 11 c（+）CD 8（+）和CD 11 c（+）CD 4（+）T细胞，Foxp 3，PD-1和CTLA-4表达的CD 4（+）T细胞和CD 8（+）T细胞，这些小鼠来自成熟小鼠和结直肠癌（CRC）小鼠。各组骨髓（BM）、脾脏和淋巴结（LN）中的CD 3（+）CD 11 c（+）T细胞分析显示，与年轻组和成熟组相比，所有组的BM和癌症组的淋巴器官中的CD 3（+）CD 11 c（+）T细胞百分比较高。小鼠BM中的CD 4（低）和CD 4（高）细胞部分对于Foxp 3和CTLA-4具有不同的表达模式。我们已经观察到，与正常小鼠相比，CRC小鼠的BM、脾脏和LN中CD 8（+）PD-1（+）T细胞的频率更高。T细胞耗竭与抑制性受体PD-1相关。根据CD 8（+）T细胞中CD 11 c表达的调节作用，我们提出表达CD 11 c、Foxp 3、CTLA-4和PD-1的T细胞百分比升高与CRC中免疫应答失调相关。
CD11c is a member of the 2-integrin family typically used to define myeloid dendritic cells (DCs). Recent reports identify CD11c-expressing CD8(+) T cells as a new subset of CD8(+) regulatory T cells (Treg). Evidence exists that CD11c(+)CD8(+) T cells may exert their effector or regulatory functions under different conditions. To date, no studies have addressed the frequency of CD11c(+) T cells in cancer. Limited evidence exists in terms of expression of immune-checkpoint receptors, programmed cell death protein 1 (PD-1) and T-lymphocyte-associated antigen 4 (CTLA-4), as well as forkhead box P3 (Foxp3) in mouse lymphoid organs. Here, we have assessed CD11c(+)CD8(+) and CD11c(+)CD4(+) T cells, Foxp3, PD-1, and CTLA-4 expressing CD4(+) T cells and CD8(+) T cells in different tissues from three groups of male BALB/c miceyoung, mature, and those with colorectal cancer (CRC). Analysis of CD3(+)CD11c(+) T cells in the bone marrow (BM), spleen, and lymph nodes (LN) in each group showed a higher percentage of CD3(+)CD11c(+) T cells in the BM from all groups and in the lymphoid organs of the cancer group compared with the young and mature groups. CD4(low) and CD4(high) cell fractions in mice BM have different expression patterns for Foxp3 and CTLA-4. We have observed a higher frequency of CD8(+)PD-1(+) T cells in the BM, spleen, and LN of CRC mice compared with normal mice. T-cell exhaustion is associated with inhibitory receptor PD-1. According to the regulatory roles of CD11c expression in CD8(+) T cells, we have proposed that the elevated percentage of CD11c, Foxp3, CTLA-4, and PD-1 expressing T cells were associated with immune response dysregulation in CRC.