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      Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature

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          Abstract

          Gamma delta T cells (Tc) are divided according to the type of Vδ and Vγ chains they express, with two major γδ Tc subsets being recognized in humans: Vδ2Vγ9 and Vδ1. Despite many studies in pathological conditions, only a few have quantified the γδ Tc subsets in healthy adults, and a comprehensive review of the factors influencing its representation in the blood is missing. Here we quantified the total γδ Tc and the Vδ2/Vγ9 and Vδ1 Tc subsets in the blood from 30 healthy, Caucasian, Portuguese adults, we characterized their immunophenotype by 8-color flow cytometry, focusing in a few relevant Tc markers (CD3/TCR-γδ, CD5, CD8), and costimulatory (CD28), cytotoxic (CD16) and adhesion (CD56) molecules, and we examined the impacts of age and gender. Additionally, we reviewed the literature on the influences of race/ethnicity, age, gender, special periods of life, past infections, diet, medications and concomitant diseases on γδ Tc and their subsets. Given the multitude of factors influencing the γδ Tc repertoire and immunophenotype and the high variation observed, caution should be taken in interpreting “abnormal” γδ Tc values and repertoire deviations, and the clinical significance of small populations of “phenotypically abnormal” γδ Tc in the blood.

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          Most cited references189

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          HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C.

          The protein HLA-E is a non-classical major histocompatibility complex (MHC) molecule of limited sequence variability. Its expression on the cell surface is regulated by the binding of peptides derived from the signal sequence of some other MHC class I molecules. Here we report the identification of ligands for HLA-E. We constructed tetramers in which recombinant HLA-E and beta2-microglobulin were refolded with an MHC leader-sequence peptide, biotinylated, and conjugated to phycoerythrin-labelled Extravidin. This HLA-E tetramer bound to natural killer (NK) cells and a small subset of T cells from peripheral blood. On transfectants, the tetramer bound to the CD94/NKG2A, CD94/NKGK2B and CD94/NKG2C NK cell receptors, but did not bind to the immunoglobulin family of NK cell receptors (KIR). Surface expression of HLA-E was enough to protect target cells from lysis by CD94/NKG2A+ NK-cell clones. A subset of HLA class I alleles has been shown to inhibit killing by CD94/NKG2A+ NK-cell clones. Only the HLA alleles that possess a leader peptide capable of upregulating HLA-E surface expression confer resistance to NK-cell-mediated lysis, implying that their action is mediated by HLA-E, the predominant ligand for the NK cell inhibitory receptor CD94/NKG2A.
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            Roles of the NKG2D immunoreceptor and its ligands.

            According to present concepts, innate immunity is regulated by receptors that determine danger levels by responding to molecules that are associated with infection or cellular distress. NKG2D is, perhaps, the best characterized receptor that is associated with responses to cellular distress, defined as transformation, infection or cell stress. This review summarizes recent findings that concern NKG2D, its ligands, its signalling properties and its role in disease, and provides a framework for considering how the induction of immune responses can be regulated by cellular responses to injury.
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              γδ T cells in cancer.

              With the promise of T cell-based therapy for cancer finally becoming reality, this Review focuses on the less-studied γδ T cell lineage and its diverse responses to tumours. γδ T cells have well-established protective roles in cancer, largely on the basis of their potent cytotoxicity and interferon-γ production. Besides this, recent studies have revealed a series of tumour-promoting functions that are linked to interleukin-17-producing γδ T cells. Here, we integrate the current knowledge from both human and mouse studies to highlight the potential of γδ T cell modulation to improve cancer immunotherapy.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                16 March 2020
                March 2020
                : 9
                : 3
                : 729
                Affiliations
                [1 ]Laboratory of Cytometry, Unit for Hematology Diagnosis, Department of Hematology, Hospital de Santo António (HSA), Centro Hospitalar Universitário do Porto (CHUP), Unidade Multidisciplinar de Investigação Biomédica, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS/UP); 4099-001 Porto Porto, Portugal; soniafonseca.hematologiaclinica@ 123456chporto.min-saude.pt (S.F.); catarinalau.hematologiaclinica@ 123456chporto.min-saude.pt (C.L.); mariateixeira.hematologiaclinica@ 123456chporto.min-saude.pt (M.d.A.T.)
                [2 ]Department of Clinical Pathology, Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/E); 4434-502 Vila Nova de Gaia, Portugal; v_lpereira@ 123456hotmail.com
                [3 ]Laboratory of Immunohematology and Blood Donors Unit, Department of Hematology, Hospital de Santo António (HSA), Centro Hospitalar Universitário do Porto (CHUP), Unidade Multidisciplinar de Investigação Biomédica, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS/UP); 4099-001Porto, Portugal; u08095@ 123456chporto.min-saude.pt
                Author notes
                [* ]Correspondence: margaridalima@ 123456chporto.min-saude.pt ; Tel.: + 351-22-20-77-500
                [†]

                These authors contributed equally to this work.

                [‡]

                These authors contributed equally to this work.

                Article
                cells-09-00729
                10.3390/cells9030729
                7140678
                32188103
                b34e1b7a-6e86-4c0f-a7bb-344563a18d32
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 February 2020
                : 13 March 2020
                Categories
                Article

                gamma delta t cells,gamma delta t cell repertoire,vdelta1,vdelta2,vgamma9,normal reference values,human herpes viruses,human cytomegalovirus,immune response

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