The Therapeutic Potential of T Cell Metabolism

Transplant rejection mediated by the adaptive immune system remains a major barrier to achieving long-term tolerance and graft survival. Emerging evidence indicates that lymphocytes rapidly shift their metabolic programs in response to activation, costimulatory, and cytokine signals to support required effector cell differentiation and function. These observations have led to the hypothesis that manipulating the metabolic programs of immune cells could serve as a powerful therapeutic strategy for attenuating deleterious immune responses and facilitating durable tolerance in the setting of allogeneic solid organ or bone marrow transplant. In this minireview, we introduce the fundamentals of metabolism, highlight the current understanding of how adaptive immune cells utilize their metabolic programs, and discuss the potential for targeting metabolism as a therapeutic approach to induce tolerance in the transplant setting.