ATP-mediated signaling of P2X7 receptors controls donor extracellular vesicle release and MHC cross-decoration after allotransplantation.

After skin allotransplantation, intercellular transfer of donor MHC molecules mediated primarily by extracellular vesicles (EVs) released by the allograft is known to contribute to semi-direct and indirect activation of alloreactive T cells involved in graft rejection. At the same time, there is ample evidence showing that initiation of adaptive alloimmunity depends on early innate inflammation caused by tissue injury and subsequent activation of myeloid cells (macrophages and dendritic cells) recognizing danger associated molecular patterns (DAMPs). Among these DAMPs, extracellular ATP plays a key role in innate inflammation through binding to P2X7 receptors.

TRACE-seq: A transgenic system for unbiased and non-invasive transcriptome profiling of living cells.

Dynamic profiling of changes in gene expression in response to stressors in specific microenvironments without requiring cellular destruction remains challenging. Current methodologies that seek to interrogate gene expression at a molecular level require sampling of cellular transcriptome and therefore lysis of the cell, preventing serial analysis of cellular transcriptome. To address this area of unmet need, we have recently developed a technology allowing transcriptomic analysis over time without cellular destruction.

T cell antigenicity and immunogenicity of allogeneic exosomes.

Extracellular vesicles, including exosomes, are regularly released by allogeneic cells after transplantation. Recipient antigen-presenting cells (APCs) capture these vesicles and subsequently display donor MHC molecules on their surface. Recent evidence suggests that activation of alloreactive T cells by the so-called cross-dressed APCs plays an important role in initiating the alloresponse associated with allograft rejection.

Emerging role of exosomes in allorecognition and allograft rejection.

Purpose Of Review: This article reviews recent literature on the nature of extracellular vesicles released by allogeneic transplants and examine their role in T-cell alloimmunity involved in rejection and tolerance of these grafts.

Recent Findings: Donor cells release extracellular vesicles, including exosomes, after transplantation of allogeneic organs and tissues. Consequently, recipient APCs take up these exosomes and present donor MHC antigens on their surface (allo-MHC cross-dressing) thus, activating some alloreactive T cells via a mechanism called semi-direct pathway of allorecognition.