Emerging role of exosomes in allorecognition and allograft rejection

Abstract

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. In addition, one study shows that exosomes carrying noninherited maternal antigens are associated with maternal microchimerism and tolerance in offspring. Finally, a few studies describe potential utilization of exosomes as modulators of alloimmunity and biomarkers of rejection in allotransplantation.

Summary: Extracellular vesicles, including exosomes, released by allografts contribute to recognition of donor antigens by T cells after allotransplantation. This occurs through cross-dressing of recipient APCs with donor MHC antigens and subsequent activation of T cells, a process called semi-direct alloreactivity. The relevance of this phenomenon in rejection and tolerance of allografts and the potential utilization of exosomes as biomarkers in transplantation are discussed.

FIGURE 1

MHC cross-dressing can promote cooperation between alloreactive CD4⁺ and CD8⁺ T cells. Panels (a) and (b) depicts two models describing how indirectly activated CD4⁺ T cells can provide help to CD8⁺ T cells after placement of a MHC class I-mismatched allograft. Panel (a) shows a classical four-cell cluster whereby CD4⁺ and CD8⁺ T cells recognize donor MHC indirectly (donor MHC peptide) and directly (intact donor MHC), respectively on distinct APCs. Panel (b) shows how donor MHC class I cross-dressing can promote CD4⁺⁻CD8⁺ T-cell cooperation by having self-MHC class II and donor peptide (indirect presentation) and donor MHC class I (direct presentation) presented on the same antigen-presenting cell (three-cell cluster).