The Functional Adaptability of Hyporesponsive T Cells and its Impact on Transplant Outcomes

The functional adaptability of hyporesponsive T cells in precluding transplant acceptance is not well recognized. This review aims to highlight the impact of this mechanism on transplant outcomes and explore potential strategies to overcome this challenge.

Hyporesponsive T cells exist in two major distinct states: anergy and exhaustion. In response to infection, alloreactive anergic T cells can differentiate into IFN-γ producing effector cells, leading to the abrogation of transplant acceptance. Depleting anergic T cells has been shown to promote transplant acceptance under infection. In addition, "precursor exhausted" T (T_PEX) cells can differentiate into effector cells during checkpoint inhibitor immunotherapy. This helps explain why using checkpoint inhibitors in transplant recipients heightens the risk of graft rejection.

This review focuses on the functional adaptability of hyporesponsive T cells and highlights the importance of further investigations into strategies to disarm these cells. Such research could have significant clinical implications for transplant patients.