Tissue Resident Memory Cells

Tissue resident memory T cells (T_RM) are a relatively newly discovered subset of memory T cells. Rather than inhabiting secondary lymphoid tissue, they are lodged in peripheral tissues. While T_RM can appear in any tissue, they are most abundant in tissues that abut the environment--skin, lung, gut, oral and vaginal mucosa. They accumulate as a result of T cell mediated inflammatory processes which occur in response to infection or encounter with a non-pathogenic antigen. Strategically, they can respond almost immediately to a subsequent encounter with the antigen for which they are specific, and thus play a critical role in host defense. CD8 T_RM specific for pathogenic viruses have been described, as well as CD4 T_RM for pathogenic fungi and other microorganisms. While T_RM play a role in host defense, inappropriate activation of T_RM in response to autoantigen or otherwise innocuous antigen is thought to play a key role in several T cell mediated inflammatory diseases, including psoriasis, spondyloarthritides, multiple sclerosis, type I diabetes, and asthma. Dislodging pathogenic T_RM from tissue has proven difficult or impossible, and thus many of these disorders are relapsing even if successfully treated. Their dependence on cytokines such as IL-15, fatty acid metabolism, and expression of CD69 may represent targets of therapeutic opportunity.