Differential Roles of Direct and Indirect Allorecognition Pathways in the Rejection of Skin and Corneal Transplants

Abstract

Background

It is generally accepted that all transplants are not rejected in the same fashion. However, the extrinsic and intrinsic factors that control the recognition and rejection of a particular allograft by the host are not well characterized.

Methods

We compared the mechanisms underlying the response to donor antigens by T cells activated after transplantation of fully allogeneic skin and corneal grafts in mice.

Results

In corneal-transplanted mice, the CD4+ T cell response was exclusively mediated by T cells recognizing minor antigens in an indirect fashion and producing low levels of IL-2. In contrast, skin grafts elicited both direct and indirect CD4+ T cell responses primarily directed to MHC antigens and characterized by high IL-2 levels. While CD8+ T cells producing γIFN were activated directly in both skin- and corneal-grafted mice, only CD8+ T cells from skin-transplanted mice mounted a cytotoxic response. Next, we investigated whether failure of corneal transplants to induce a CD4+ direct alloresponse is due to their poor immunogenicity or to the site of placement (eye). We observed that corneas transplanted under the skin as well as splenocytes transplanted in the eye were both capable of inducing direct CD4+ T cell alloreactivity.

Conclusions

This shows that, failure of orthotopic corneal allotransplants to elicit a CD4+ T cell direct alloresponse is associated with the combination of two factors, their low immunogenicity and the immune-privileged properties of the eye.