Ablation of pathogenic memory T-cell responses by bone marrow-mediated gene therapy under immune-preserving conditions

R. Steptoe, J. Al-Kouba, M. Coleman, C. Jessup, M. Starkey, N. Overgaard, J. Bridge, J. Horvat, R. Werder, S. Walters, P. T. Coates, S. Grey, R. Thomas, J. Wells, P. Hansbro, S. Phipps, J. Davies

    Research output: Contribution to journalMeeting Abstractpeer-review


    Established memory T cell responses represent a key hurdle to both protein and tissue replacement therapies as well as the application of tolerogenic immunotherapies in general. Targeting expression of antigen to antigen-presenting cells is a powerful means to induce T-cell tolerance. We have shown previously that genetic targeting of antigens to DC and other APC inactivates memory CD4+ andCD8+ T cells, but we now show this can be exploited for induction of therapeutic tolerance to 'turn-off' established but unwanted T-cell responses. We have combine the approaches of targeted antigen expression and bone marrow (BM) / hematopoietic stem cell transplantation under immune-preserving conditions to show antigen-specific, therapeutic termination of memory CD4+ and CD8+ T-cell responses. This approach has the capacity to turn off the pathogenic T-cell responses that underlie autoimmune rejection of antigen-expressing pancreatic islet transplants and Th2-mediated airwaysinflammation. Associated with this immune-related pathology related to these responses, such asairways inflammation and hyper-responsiveness is prevented or ameliorated. Immunologicalmechanisms associated with reversal of established memory T-cell responses by BM transfer underimmune preserving conditions appear to be deletion and induction of unresponsiveness through T-cell'adaption'. Refinement of BM-mediated gene therapy for tolerance such as this could lead todevelopment of highly-effective therapies for T-cell mediated pathologies.
    Original languageEnglish
    Article number755
    Pages (from-to)722
    Number of pages1
    JournalEuropean Journal of Immunology
    Issue numberS1
    Publication statusPublished - Aug 2016
    EventInternational Congress of Immunology (ICI) -
    Duration: 21 Aug 2016 → …


    • Ablation
    • pathogenic
    • memory
    • T-cell
    • bone marrow
    • mediated gene therapy
    • immune
    • preserving


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