Jigesh A. Shah

This report describes liver transplantation as a successful strategy in the management of a young man who presented to a local emergency room following catastrophic traumatic hepatic vascular injuries. Expeditious multidisciplinary management, including interventional radiology, trauma surgery, and ultimately transplant surgery, provided the patient with definitive therapy following his injuries and early return to normal activity. Our experience highlights the importance of prompt referral of select hepatic trauma patients for liver transplant evaluation as part of their complex trauma management.

Regulatory T cells (Treg) play an important role in modulating the immune response and has attracted increasing attention in diverse fields such as cancer treatment, transplantation and autoimmune diseases. CC chemokine receptor 4 (CCR4) is expressed on the majority of Tregs, especially on effector Tregs. Recently we have developed a diphtheria‐toxin based anti‐human CCR4 immunotoxin for depleting CCR4+ cells in vivo. In this study, we demonstrated that the anti‐human CCR4 immunotoxin bound and depleted monkey CCR4+ cells in vitro. We also demonstrated that the immunotoxin bound to the CCR4+Foxp3+ monkey Tregs in vitro. In vivo studies performed in two naive cynomolgus monkeys revealed 78–89% CCR4+Foxp3+ Treg depletion in peripheral blood lasting approximately 10 days. In lymph nodes, 89–96% CCR4+Foxp3+ Tregs were depleted. No effect was observed in other cell populations including CD8+ T cells, other CD4+ T cells, B cells and NK cells. To our knowledge, this is the first agent that effectively depleted non‐human primate (NHP) Tregs. This immunotoxin has potential to deplete effector Tregs for combined cancer treatment.

Xenotransplantation remains the best near-term solution to the shortage of transplantable organs that currently limits the field of transplantation. However, because the immune response to xenografts is considerably stronger than it is to allografts, the amount of non-specific immunosuppression required to avoid xenograft rejection may limit clinical applicability. For this reason, we consider it likely that the success of clinical xenotransplantation will depend on finding ways of safely inducing tolerance across xenogeneic barriers rather than relying entirely on non-specific immunosuppressive agents. In this laboratory, two approaches are being studied for the induction of pig-to-primate tolerance: a) the simultaneous transplantation of vascularized thymus and solid organs; and b) mixed hematopoietic chimerism. A summary of the development of these two approaches and their current status is the subject of this review.