Extracellular vesicles in fetal-maternal immune tolerance.

Two key problems of allo-tolerance during fetal-maternal co-existence are: 1) it's focus must be local, allowing the mother's continued peripheral immune competence to resist pathogens ubiquitously, and 2) it must propagate itself, i.e. continuously recruit new re-enforcements of the local tolerant state.

The potential role of infusions of T regulatory cells in inducing and maintaining liver allograft tolerance.

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Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.

Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection.

Extracellular Vesicle-associated GARP/TGFβ:LAP Mediates "Infectious" Allo-tolerance.

Unlabelled: Here we test the hypothesis that, like CD81-associated "latent" IL35, the transforming growth factor (TGF)β:latency-associated peptide (LAP)/glycoprotein A repetitions predominant (GARP) complex was also tethered to small extracellular vesicles (sEVs), aka exosomes, produced by lymphocytes from allo-tolerized mice. Once these sEVs are taken up by conventional T cells, we also test whether TGFβ could be activated suppressing the local immune response.

Methods: C57BL/6 mice were tolerized by i.

Cross-decoration of dendritic cells by non-inherited maternal antigen-containing extracellular vesicles: Potential mechanism for PD-L1-based tolerance in cord blood and organ transplantation.

Exposure to non-inherited maternal antigens (NIMA) during the fetal period induces lifelong split tolerance to grafts expressing these allo-antigens. In adult mice, the production of extracellular vesicles (EVs) from maternal microchimeric cells causes cross-decoration (XD) of offspring dendritic cells (DC) with NIMA and upregulation of PD-L1, contributing to NIMA tolerance. To see how this may apply to humans, we tested NIMA acquisition by fetal DCS in human cord blood.