The Interplay between Innate Immune Memory and Adaptive Immunity: Emerging Mechanisms in Alloimmunity

Innate immune memory is increasingly recognized as a regulator of immune responses in solid organ transplantation. Following an initial stimulus, innate immune cells and their progenitors can undergo epigenetic and metabolic reprogramming, resulting in enhanced or suppressed pro-inflammatory responses upon subsequent encounters, termed trained immunity and innate immune tolerance, respectively. These antigen-independent forms of innate immune memory are complemented by donor-specific innate immune memory. Importantly, innate immune memory may influence alloimmune responses by shaping adaptive T cell activation through altered cytokine production, antigen presentation, and co-stimulatory signals. Conversely, adaptive immune cells can regulate the induction of innate immune memory, highlighting a bidirectional innate-adaptive crosstalk. In this review, we discuss the interplay of innate immune memory with adaptive immunity, and the potential to harness this mechanism to promote graft survival and long-term tolerance.