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    Cytomegalovirus replication is associated with enrichment of distinct g 8 T cell subsets following lung transplantation: A novel therapeutic approach?

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    Author
    Stankovic, S; Davey, MS; Shaw, EM; von Borstel, A; Cristiano, Y; Levvey, BJ; Rossjohn, J; Westall, GP; Snell, GI; Brooks, AG; ...
    Date
    2020-11-01
    Source Title
    Journal of Heart and Lung Transplantation
    Publisher
    ELSEVIER SCIENCE INC
    University of Melbourne Author/s
    Sullivan, Lucy; Stankovic, Sanda; Brooks, Andrew; Rossjohn, Jamie
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Stankovic, S., Davey, M. S., Shaw, E. M., von Borstel, A., Cristiano, Y., Levvey, B. J., Rossjohn, J., Westall, G. P., Snell, G. I., Brooks, A. G. & Sullivan, L. C. (2020). Cytomegalovirus replication is associated with enrichment of distinct g 8 T cell subsets following lung transplantation: A novel therapeutic approach?. JOURNAL OF HEART AND LUNG TRANSPLANTATION, 39 (11), pp.1300-1312. https://doi.org/10.1016/j.healun.2020.08.014.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/254547
    DOI
    10.1016/j.healun.2020.08.014
    Open Access URL
    https://europepmc.org/articles/PMC7448790?pdf=render
    Abstract
    BACKGROUND: Anti-viral treatments to control cytomegalovirus (CMV) after lung transplantation (LTx) are associated with toxicity and anti-viral resistance. Cellular immunotherapy with virus-specific cytotoxic T cells has yielded promising results but requires donor/recipient matching. γδ T cells are involved in anti-viral immunity and can recognize antigens independently of major histocompatibility complex molecules and may not require the same level of matching. We assessed the phenotype of circulating γδ T cells after LTx to identify the candidate populations for CMV immunotherapy. METHODS: Peripheral blood mononuclear cells were isolated from lung transplant recipients before transplantation and at routine bronchoscopies after LTx. Patients were stratified by risk of CMV disease into moderate risk (recipient CMV seropositive, n = 15) or high risk (HR) (recipient CMV seronegative/donor CMV seropositive, n = 10). CMV replication was classified as polymerase chain reaction positive (>150 copies/ml) in blood and/or bronchoalveolar lavage within the first 18 months. The phenotype of γδ T cells was assessed by multicolor flow cytometry, and T-cell receptor (TCR) sequences were determined by deep sequencing. RESULTS: In HR lung transplant recipients with CMV replication, we observed striking phenotypic changes in γδ T cells, marked by an increase in the proportion of effector Vδ1+ γδ T cells expressing the activating natural killer cell receptor NKG2C. Moreover, we observed a remarkable increase in TCR diversity. CONCLUSIONS: NKG2C+ Vδ1+ γδ T cells were associated with CMV replication and may indicate their potential to control infection. As such, we propose that they could be a potential target for cellular therapy against CMV.

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