γδ T Cell Subsets Based on Structure

T lymphocytes can be divided into 2 populations: αβ T and γδ T cells. They are distinguished by the structure of their cell receptors. The αβ T cell receptors (TCR) are composed of α and β chains and the γδ TCRs are composed of γ and δ chains. αβ T cells account for a majority of T lymphocytes in peripheral blood, while γδ T cells only account for 1-5%.

Fig.1 Tumor cell ligands recognized by human γδ T cells and strategies for γδ T cell-based immunotherapy. (Kabelitz, 2007)

Human γδ T cells are divided into three types based on the differences of TCR δ-chain: Vδ1 γδ T cells, Vδ2 γδT cells, and other γδ T cells subsets. Different γδ T cell subsets act as different functions in the progression of diseases.

• Vδ1+ γδ T cells

Human Vδ1+ γδ T cells are primarily found in the skin, small intestine, and other mucosal tissues. A small amount of Vδ1+ γδ T cells is also found in the spleen and liver. Vδ1+ γδ T cells contain diverse Vγ chains such as Vγ2, Vγ3, Vγ4, Vγ5, Vγ8, and Vγ10. They account for less than 30% of γδ T cells in peripheral blood.

• Vδ2+ γδ T cells

Vδ2+ γδ T cells are mainly Vγ9Vδ2 T cells whose receptors consist of Vδ2 and Vγ9 chains. They account for more than 70% of γδ T cells in peripheral blood. Vγ9Vδ2 T cells have been indicated to inhibit tumor cell proliferation and promote tumor cell apoptosis, thus providing a promising candidate for anti-tumor immunotherapy.

• Other γδ T Cells Subsets

Other γδ T cells subsets mainly contain Vδ3 and Vδ4 T cells. Vδ3 T cells consist of the majority of non-Vδ1 and non-Vγ9Vδ2 γδT cells. Vδ5 T cells whose receptors are composed of Vγ4 and Vδ5 chains are mainly found in peripheral blood. Vδ5 Vγ4 T cells can recognize endothelial protein C receptor (EPCR) on CMV-infected epithelial cells and epithelial tumor cells via TCR.

Table.1 Feature of human γδ T cell subsets. (Liu, 2020)

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References

1. Kabelitz, D.; et al. Perspectives of γδ T cells in tumor immunology. Cancer Res. 2007, 67(1): 5-8.
2. Liu, Y.; Zhang, C. The role of human γδ T cells in anti-tumor immunity and their potential for cancer immunotherapy. Cells. 2020, 9: 1206