Figure 3. Potential impacts of reduced material immunogenicity and improved cell implant viability on immune pathways in pancreatic islet transplantation.

(1) Direct antigen presentation is retained for non-immunoisolatory, vascularized scaffolds. Approaches focused on improving donor cell viability post-transplantation, through vascularization, optimized 3-D material implants, and/or material-driven oxygen supplementation can result in reduced (2) donor cell death or change in the cell death pathway, which reduces DAMPs and/or shed antigen. (3) Antigen uptake and processing can be modified in the absence of DAMPs, leading to skewing of the phenotype of the innate APCs involved in the (4) indirect antigen presentation. APC phenotype shift can alter interactions with T lymphocytes and abrogate their activation. (5) Direct cell-mediated killing and the (6) cytokine-induced cell death can be mediated through the direct pathway only. Due to decreased T cell activation in the indirect pathway, (7) CD4+ T cell-mediated B cell activation, (8) antibody class switching, (9) production of donor-specific antibodies, and (10) antibody-mediated graft destruction can also be minimized.