A dual nature of γδ T cell immune memory responses

Immune memory was considered for decades an exclusive hallmark of the adaptive immune response. However, recent studies have revealed that innate immune cells can also 'recall' information of a primary insult during infection or vaccination and deploy robust antigen-agonistic immune reactivity upon secondary challenge. This de-facto innate immune memory response is designated as 'trained immunity'. γδ T cells are unconventional T cells that possess unique immunologic features of both adaptive and innate immunity. Their immune memory responses to various bacterial and viral agents were originally described to be of an adaptive immune nature. Nevertheless, growing evidence shows that γδ T cells can also mount antigen-independent memory responses resembling trained immunity. In this review, we discuss the dual nature of immune memory responses of γδ T cells and provide insights into their important role in protection against bacterial, viral, and parasitic infections in humans and animals.