The emerging role of effector functions exerted by tissue-resident memory T cells.

The magnitude of the effector functions of memory T cells determines the consequences of the protection against invading pathogens and tumor development or the pathogenesis of autoimmune and allergic diseases. Tissue-resident memory T cells (T_RM cells) are unique T-cell populations that persist in tissues for long periods awaiting re-encounter with their cognate antigen. Although T_RM cell reactivation primarily requires the presentation of cognate antigens, recent evidence has shown that, in addition to the conventional concept, T_RM cells can be reactivated without the presentation of cognate antigens. Non-cognate T_RM cell activation is triggered by cross-reactive antigens or by several combinations of cytokines, including interleukin (IL)-2, IL-7, IL-12, IL-15 and IL-18. The activation mode of T_RM cells reinforces their cytotoxic activity and promotes the secretion of effector cytokines (such as interferon-gamma and tumor necrosis factor-alpha). This review highlights the key features of T_RM cell maintenance and reactivation and discusses the importance of effector functions that T_RM cells exert upon being presented with cognate and/or non-cognate antigens, as well as cytokines secreted by T_RM and non-T_RM cells within the tissue microenvironment.