*Purpose: Cellular therapy is an emerging treatment in the field of clinical transplantation with the potential to improve both short and long-term transplant outcomes. We are taking the first steps towards assessing the potential of cell therapies in the clinical setting of living donor kidney transplantation. A critical aspect of these studies is generating an understanding of how infused cell therapies might impact on the recipient immune response to alloantigen and mediate any beneficial effect.

*Methods: Patients receiving regulatory T cell infusion as part of a phase 1 clinical trial underwent a protocol biopsy at 8 months post-transplant. Biopsies are compared with those from patients with an acute T cell mediated rejection episode and surveillance biopsies from patients with clinically stable graft function. Initial analysis was performed using routine immunohistochemistry. Subsequently, a NanoString GeoMX digital spatial profiler was used to interrogate the composition of biopsy infiltrates through protein and mRNA expression in a tissue location specific manner (Figure 1).

*Results: Routine histology demonstrated the presence of unique cellular infiltrates that were dense and remarkably focal in nature in all patients treated with cell therapy. Immunohistochemistry revealed between 5 and 10% of such infiltrates are positive for FOXP3, a marker of regulatory T cells, but one that is also expressed on activated human effector T cells. Digital spacial profiling revealed that infiltrates in all three clinical scenarios demonstrate unique properties based on protein and mRNA expression data and represent distinct cell populations. Infiltrates in the setting of cellular therapy have an expression profile suggestive of regulatory activity.

*Conclusions: We demonstrate the prescence of dense focal cellular infiltrates in renal transplant biopsies from patients treated with cell therapy. Such infiltrates are interogated using novel spatial profiling techniques and found to be distinct from those seen during a rejection episode and from infiltrates noted on surveillance biopsies.

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