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

Abstract

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. CD4low and CD4high 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.