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Assays designed to select transplant recipients for immunosuppression withdrawal have met with limited success, perhaps because they measure events downstream of T cell-alloantigen interactions. Using in vitro time-lapse microscopy in a mouse transplant model, we investigated whether transplant outcome would result in changes in the proportion of CD4(+) T cells forming prolonged interactions with donor dendritic cells. By blocking CD4-MHC class II and CD28-B7 interactions, we defined immunologically relevant interactions as those ≥500 s. Using this threshold, T cell-dendritic cell (T-DC) interactions were examined in rejection, tolerance and T cell control mediated by regulatory T cells. The frequency of T-DC contacts ≥500 s increased with T cells from mice during acute rejection and decreased with T cells from mice rendered unresponsive to alloantigen. Regulatory T cells reduced prolonged T-DC contacts. Importantly, this effect was replicated with human polyclonally expanded naturally occurring regulatory T cells, which we have previously shown can control rejection of human tissues in humanized mouse models. Finally, in a proof-of-concept translational context, we were able to visualize differential allogeneic immune synapse formation in polyclonal CD4(+) T cells using high-throughput imaging flow cytometry.

Original publication




Journal article


American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

Publication Date





1394 - 1407


Toronto Lung Transplant Program and Division of Respirology, Department of Medicine, University Health Network and University of Toronto, Toronto, Ontario, Canada.


Dendritic Cells, CD4-Positive T-Lymphocytes, Animals, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Isoantigens, Heart Transplantation, Immune Tolerance, Graft Rejection, Graft Survival, T-Lymphocytes, Regulatory, Immunological Synapses, Time-Lapse Imaging