The primary function of the immune system is to protect the host from infectious microorganisms and cancers. However, a major component of the immune response involves the direct elimination of cells in the body and the induction of systemic inflammation, which may result in life-threatening immunopathology. Therefore, the immune system has developed complex mechanisms to regulate itself with a specialized subset of CD4 T lymphocytes (referred to as regulatory T cells) and immune checkpoint pathways, such as the programmed cell death protein 1 pathway. These immune regulatory mechanisms can be exploited by pathogens and tumours to establish persistence in the host, warranting a deeper understanding of how to fine-tune immune responses during these chronic diseases. Here, I discuss various features of immune regulatory pathways and what important aspects must be considered in the next generation of therapies to reverse immune exhaustion, understanding that this process is a natural mechanism to prevent the host from destroying itself.
Keywords: immune checkpoints; immune exhaustion; immune memory; lymphocytic choriomeningitis virus; regulatory T cells.
© 2017 John Wiley & Sons Ltd.