Concise review: immunologic lessons from solid organ transplantation for stem cell-based therapies

Abstract

Clinical organ transplantation became possible only after powerful immunosuppressive drugs became available to suppress the alloimmune response. After decades of solid organ transplantation, organ rejection is still a major challenge. However, significant insight into allorecognition has emerged from this vast experience and should be used to inform future stem cell-based therapies. For this reason, we review the current understanding of selected topics in transplant immunology that have not been prominent in the stem cell literature, including immune responses to ischemia/reperfusion injuries, natural killer cells, the adaptive immune response, some unresolved issues in T-cell allorecognition, costimulatory molecules, and the anticipated role of regulatory T cells in graft tolerance.

Figure 1.

Nonprofessional and professional, direct and indirect presentation of antigen-initiated alloimmune responses. 1: Auto- and allocellular interactions can contribute to transplant alloresponses. In the liver, vascular endothelial cells can function as nonprofessional APCs. In direct presentation of allopeptides (2a) professional APCs are donor-derived dendritic cells that present allopeptides and interact with T cells. Indirect presentation is by recipient APCs that take up debris from the graft and present allopeptides (2b). In T-cell priming by nonprofessional APCs, recipient T cells migrate into the donor organ and interact with MHC and costimulatory molecules (CD80) presented by vascular endothelial cells activated by interferon-γ. 2a: Direct presentation. Donor-derived APCs (blue) migrate out of the organ into secondary lymphoid organs, where they interact with recipient CD4 or CD8 T cells. The MHC molecules are of the donor genotype (allo) and present allopeptides (shown in blue). 2b: Indirect presentation. Recipient APCs (pink) circulate to the donor, where they phagocytose debris of apoptotic or necrotic donor cells (blue). The APCs migrate out of the donor organ into the draining lymph node, where they interact with recipient CD4 or CD8 T cells. The MHC molecules on these APCs are of the recipient genotype, and they present allopeptides (blue). The inset shows an enlarged, labeled version of the components of the presentation complex. Abbreviations: APC, antigen-presenting cell; MHCI, major histocompatibility complex class I; MHCII, major histocompatibility complex class II.