CD27^-CD45⁺ γδ T cells can be divided into two populations, CD27^-CD45^int and CD27^-CD45^hi with little proliferation potential

In addition to the majority of T cells which carry the αβ T cell receptor (TCR) for antigen, a distinct subset of about 1–5% of human peripheral blood T cells expressing the γδ TCR contributes to immune responses to infection, tissue damage and cancer. T cells with the Vδ2⁺ TCR, usually paired with Vγ9, constitute the majority of these γδ T cells. Analogous to αβ T cells, they can be sorted into naive (CD27⁺CD45RA⁺), central memory (CD27⁺CD45RA⁻), effector memory (CD27⁻CD45RA⁻), and terminally-differentiated effector memory (CD27⁻CD45RA⁺) phenotypes. Here, we found that CD27⁻CD45RA⁺ γδ T cells can be further divided into two populations based on the level of expression of CD45RA: CD27⁻CD45RA^int and CD27⁻CD45RA^hi. Those with the CD27⁻CD45RA^hi phenotype lack extensive proliferative capacity, while those with the CD27⁻CD45RA^int phenotype can be easily expanded by culture with zoledronate and IL-2. These CD27^-CD45RA^hi potentially exhausted γδ T cells were found predominantly in cancer patients but also in healthy subjects. We conclude that γδ T cells can be divided into at least 5 subsets enabling discrimination of γδ T cells with poor proliferative capacity. It was one of our goals to predict the feasibility of γδ T cell expansion to sufficient amounts for adoptive immunotherapy without the necessity for conducting small-scale culture tests. Fulfilling the ≥1.5% criterion for γδ T cells with phenotypes other than CD27⁻CD45RA^hi, may help avoid small-scale culture testing and shorten the preparation period for adoptive γδ T cells by 10 days, which may be beneficial for patients with advanced cancer. - Highlights: • CD27^-CD45⁺ γδ T cells can be divided into two populations, CD27^-CD45^hi and CD27^-CD45^int. • CD27^-CD45^hi γδ T cells are detected in the peripheral blood of both cancer patients and healthy subjects. • CD27^-CD45^hi γδ T cells are distinct from so-called terminally differentiated CD27^-CD45^int γδ T cells. • CD27^-CD45^hi γδ T cells lack vigorous proliferative potential.