Abstract
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.