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.

Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

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).