The role of circulating T cells with a tissue resident phenotype (ex-T) in health and disease.

Tissue-resident memory T cells (T) are long-lived memory lymphocytes that persist in non-lymphoid tissues and provide the first line of defence against invading pathogens. They adapt to their environment in a tissue-specific manner, exerting effective pathogen control through a diverse T cell receptor (TCR) repertoire and the expression of proinflammatory cytokines and cytolytic proteins. More recently, several studies have indicated that T can egress from the tissue into the blood as so-called "ex-T", or "circulating cells with a T phenotype". The numerically small ex-T population can re-differentiate in the circulation, giving rise to new memory and effector T cells. Following their egress, ex-T in the blood and secondary lymphoid organs can be identified based on their continued expression of the residency marker CD103, alongside other T-like features. Currently, it is unclear whether exit is a stochastic process, or is actively triggered in response to unknown factors. Also, it is not known whether a subset or all T are able to egress. Ex-T may be beneficial in health, as mobilisation of specialised T and their recruitment to both their site of origin as well as distant tissues results in an efficient distribution of the immune response. However, there is emerging evidence of a pathogenic role for ex-T with a suggestion that they may perpetuate both local and distant tissue inflammation. Here, we review the evidence for the existence of ex-T and examine their potential involvement in disease pathogenesis.