**11. Future perspective**

Immunity, regulation, graft rejection versus acceptance, and tolerance have proven to be extraordinarily complex. Indeed, currently used drugs and treatment protocols that are largely directed at inhibiting alloreactive T cells, have not optimally improved allograft survival or function. The tremendous progress made in understanding the molecular and cellular basis of allograft rejection has not yet been translated into durable modalities that have advanced clinical care and outcomes. Despite the many advances in both immunological knowledge and the practical application of clinical immunosuppression, the holy grail of indefinite graft survival with immune tolerance in clinical solid organ transplantation remains a distant dream. The current challenge is to integrate molecular, cellular, and anatomic concepts to achieve the equivalent of a unified field theory of the immune response to organ transplantation. A shift in emphasis, focusing on underappreciated immune pathways must now be considered to make further improvement. We highlight 3 areas of recent interest, complement, NK cells and lymphatics[35, 36], which reinforce the concept that the transplant community must direct attention on how the immune system as a whole responds to a transplant. Discoveries of new molecules, cell populations, functions or pathways have each led to the hope that the field has finally reached the point that reliable immune manipulation can now be achieved. Once that perspective is gained, we may finally be poised to make the major leaps forward in clinical care and outcomes.

#### **12. References**


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