CD27-CD45+ γδ T cells can be divided into two populations, CD27-CD45int and CD27-CD45hi with little proliferation potential

Abstract

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−CD45RAint and CD27−CD45RAhi. Those with the CD27−CD45RAhi phenotype lack extensive proliferative capacity, while those with the CD27−CD45RAint phenotype can be easily expanded by culture with zoledronate and IL-2. These CD27-CD45RAhi 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−CD45RAhi, 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.