Altered frequency of CD8 + CD11c + T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer.

CD11c is a member of the β2-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 mice-young, 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.
(© 2019 Wiley Periodicals, Inc.)