title: CD27(-)CD45(+) γδ T cells can be divided into two populations, CD27(-)CD45(int) and CD27(-)CD45(hi) 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(-)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.
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan; MEDINET Co. Ltd., Yokohama 222-0033, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Odaira
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan; MEDINET Co. Ltd., Yokohama 222-0033, Japan.
authors.forename: Shin-Nosuke
authors.initials: SN
authors.lastname: Kimura
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan; MEDINET Co. Ltd., Yokohama 222-0033, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Fujieda
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan; MEDINET Co. Ltd., Yokohama 222-0033, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan; MEDINET Co. Ltd., Yokohama 222-0033, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kambara
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan; MEDINET Co. Ltd., Yokohama 222-0033, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan; MEDINET Co. Ltd., Yokohama 222-0033, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan. Electronic address: kakimi@m.u-tokyo.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakimi
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens
keywords: Zoledronate; γδ T cell