Organ-specific differences in achieving tolerance

Abstract

Purpose of review When it comes to tolerance induction, kidney allografts behave differently from heart allografts which behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol. Recent findings Allograft tolerance has been achieved in experimental and clinical kidney transplantation. However, inducing tolerance in experimental recipients of heart and lung allografts has proven to be more challenging. New protocols being developed in nonhuman primates based on mixed chimerism and co-transplantation of tolerogenic organs may provide mechanistic insights to help overcome these challenges. Summary Tolerance induction protocols that are successful in patients transplanted with “tolerance-prone” organs such as kidneys and livers will most likely not succeed in recipients of “tolerance-resistant” organs such as hearts and lungs. Separate clinical trials using more robust tolerance protocols will be required to achieve tolerance in heart and lung recipients.

Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy

“…This notion of organ-specific differences in immune-modulatory properties is well known in the field of transplant immunology, where kidney and liver transplants require far less immune-suppression than lungs and hearts to prevent rejection. 43 Therefore, it is feasible that the immune-modulatory response from RT is also organ-dependent, as our analysis suggests. Notably, three of the CRs had primary melanoma, yielding a 30% CR rate (3 of 10 evaluable patients) for melanoma patients (0-22% in prior reports 3,10,35 ).…”

The effects of brain death and ischemia on tolerance induction are organ-specific

“…However, when heart and kidney allografts from the same MHC-mismatched donor were co-transplanted under a 12-day course of tacrolimus, recipients uniformly became tolerant of both organs (5). These studies demonstrate that the ability of a particular tolerance protocol to induce long-term unresponsiveness is organ-specific (6). …”

“…5 These studies demonstrate that the ability of a particular tolerance protocol to induce long-term unresponsiveness is organ-specific. 6 Given the striking organ-specific differences we have observed in the ability of tolerance-induction protocols to achieve immune unresponsiveness, we asked whether the effects of brain death and ischemia on tolerance induction would also differ depending on the organ transplanted. Here we show that in contrast to lung allograft recipients, donor brain death and prolonged organ ischemia did not prevent tolerance induction in isolated kidney or heart plus kidney allograft recipients.…”

Advances in the immunology of heart transplantation

“…Some organs, such as kidney and liver, are tolerance-prone, whereas others, such as heart and lung, are tolerance-resistant. 58 …”