A dual nature of γδ T cell immune memory responses

Abstract

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.

Keywords: gamma delta T cells; immune memory; immunology; inflammation; trained immunity.

Figure 1.. Schematic representation of adaptive vs. innate immune memory characteristics.

Myeloid cells and lymphocytes mount immune memory responses characterized by the enhanced effector function upon secondary exposure. While innate immune cells produce more inflammatory cytokines upon secondary challenge with heterologous stimuli, adaptive memory immune cells rapidly proliferate and generate copious amounts of antibodies and cytokines upon rechallenge with the same antigen. Antibodies, as well as memory B cells and T cells, persist in the host while cytokines produced by innate immune cells return to the baseline after the resolution of infection. Innate immune memory lasts relatively shorter than adaptive immune memory. Both adaptive and innate immune memory formation is accompanied by epigenetics and metabolic rewiring, facilitating transcriptional responses and allowing more robust immune reactions upon secondary challenge. TCR: T-cell receptor, BCR: B-cell receptor. Created with BioRender.com.