11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The complex existence of γδ T cells following transplantation: the good, the bad and the simply confusing

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Gamma delta (γδ) T cells are a highly heterogeneous population of lymphocytes that exhibit innate and adaptive immune properties. Despite comprising the majority of residing lymphocytes in many organs, the role of γδ T cells in transplantation outcomes is under‐researched. γδ T cells can recognise a diverse array of ligands and exert disparate effector functions. As such, they may potentially contribute to both allograft acceptance and rejection, as well as impacting on infection and post‐transplant malignancy. Here, we review the current literature on the role and function of γδ T cells following solid organ and hematopoietic stem cell transplantation.

          Related collections

          Most cited references77

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          NKG2D and Its Ligands: “One for All, All for One”

          The activating receptor NKG2D is peculiar in its capability to bind to numerous and highly diversified MHC class I-like self-molecules. These ligands are poorly expressed on normal cells but can be induced on damaged, transformed or infected cells, with the final NKG2D ligand expression resulting from multiple levels of regulation. Although redundant molecular mechanisms can converge in the regulation of all NKG2D ligands, different stimuli can induce specific cellular responses, leading to the expression of one or few ligands. A large body of evidence demonstrates that NK cell activation can be triggered by different NKG2D ligands, often expressed on the same cell, suggesting a functional redundancy of these molecules. However, since a number of evasion mechanisms can reduce membrane expression of these molecules both on virus-infected and tumor cells, the co-expression of different ligands and/or the presence of allelic forms of the same ligand guarantee NKG2D activation in various stressful conditions and cell contexts. Noteworthy, NKG2D ligands can differ in their ability to down-modulate NKG2D membrane expression in human NK cells supporting the idea that NKG2D transduces different signals upon binding various ligands. Moreover, whether proteolytically shed and exosome-associated soluble NKG2D ligands share with their membrane-bound counterparts the same ability to induce NKG2D-mediated signaling is still a matter of debate. Here, we will review recent studies on the NKG2D/NKG2D ligand biology to summarize and discuss the redundancy and/or diversity in ligand expression, regulation, and receptor specificity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Long-term expansion of effector/memory Vdelta2-gammadelta T cells is a specific blood signature of CMV infection.

            The ability of human gammadelta T cells to develop immunologic memory is still a matter of debate. We previously demonstrated the involvement of Vdelta2- gammadelta T lymphocytes in the response of immunosuppressed organ recipients to cytomegalovirus (CMV). Here, we demonstrate their ability to mount an adaptive immune response to CMV in immunocompetent subjects. Vdelta2- gammadelta T-cell peripheral blood numbers, repertoire restriction, and cytotoxicity against CMV-infected fibroblasts were markedly increased in CMV-seropositive, compared with CMV-seronegative, healthy persons. Whereas Vdelta2- gammadelta T cells were found as naive cells in CMV- patients, they virtually all exhibited the cytotoxic effector/memory phenotype in CMV+ patients, which is also observed in transplanted patients challenged with CMV. This long-term complete remodeling of the Vdelta2- gammadelta T-cell population by CMV predicts their ability to exhibit an adaptive anti-CMV immune response. Consistent with this, we observed that the secondary response to CMV was associated with a faster gammadelta T-cell expansion and a better resolution of infection than the primary response. In conclusion, the increased level of effector-memory Vdelta2- gammadelta T cells in the peripheral blood is a specific signature of an adaptive immune response to CMV infection of both immunocompetent and immunosuppressed patients.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia.

              Human cytomegalovirus (CMV) infections and relapse of disease remain major problems after allogeneic stem cell transplantation (allo-SCT), in particular in combination with CMV-negative donors or cordblood transplantations. Recent data suggest a paradoxical association between CMV reactivation after allo-SCT and reduced leukemic relapse. Given the potential of Vδ2-negative γδT cells to recognize CMV-infected cells and tumor cells, the molecular biology of distinct γδT-cell subsets expanding during CMV reactivation after allo-SCT was investigated. Vδ2(neg) γδT-cell expansions after CMV reactivation were observed not only with conventional but also cordblood donors. Expanded γδT cells were capable of recognizing both CMV-infected cells and primary leukemic blasts. CMV and leukemia reactivity were restricted to the same clonal population, whereas other Vδ2(neg) T cells interact with dendritic cells (DCs). Cloned Vδ1 T-cell receptors (TCRs) mediated leukemia reactivity and DC interactions, but surprisingly not CMV reactivity. Interestingly, CD8αα expression appeared to be a signature of γδT cells after CMV exposure. However, functionally, CD8αα was primarily important in combination with selected leukemia-reactive Vδ1 TCRs, demonstrating for the first time a co-stimulatory role of CD8αα for distinct γδTCRs. Based on these observations, we advocate the exploration of adoptive transfer of unmodified Vδ2(neg) γδT cells after allo-SCT to tackle CMV reactivation and residual leukemic blasts, as well as application of leukemia-reactive Vδ1 TCR-engineered T cells as alternative therapeutic tools.
                Bookmark

                Author and article information

                Contributors
                lcsull@unimelb.edu.au
                Journal
                Clin Transl Immunology
                Clin Transl Immunology
                10.1002/(ISSN)2050-0068
                CTI2
                Clinical & Translational Immunology
                John Wiley and Sons Inc. (Hoboken )
                2050-0068
                17 September 2019
                2019
                : 8
                : 9 ( doiID: 10.1002/cti2.2019.8.issue-9 )
                : e1078
                Affiliations
                [ 1 ] Department of Microbiology and Immunology The University of Melbourne at The Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia
                [ 2 ] Lung Transplant Service The Alfred Hospital Melbourne VIC Australia
                Author notes
                [*] [* ] Correspondence

                LC Sullivan, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.

                E‐mail: lcsull@ 123456unimelb.edu.au

                Article
                CTI21078
                10.1002/cti2.1078
                6748302
                64951756-b01b-4d27-b813-989c17b25030
                © 2019 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 May 2019
                : 05 August 2019
                : 05 August 2019
                Page count
                Figures: 1, Tables: 2, Pages: 10, Words: 7267
                Categories
                Special Feature Review
                Special Feature Reviews
                Custom metadata
                2.0
                cti21078
                2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:17.09.2019

                gamma delta t cells,transplant immunology,graft‐versus‐host disease

                Comments

                Comment on this article