The Role of CD4 ⁺ Resident Memory T Cells in Local Immunity in the Mucosal Tissue – Protection Versus Pathology –

Memory T cells are crucial for both local and systemic protection against pathogens over a long period of time. Three major subsets of memory T cells; effector memory T (T _EM) cells, central memory T (T _CM) cells, and tissue-resident memory T (T _RM) cells have been identified. The most recently identified subset, T _RM cells, is characterized by the expression of the C-type lectin CD69 and/or the integrin CD103. T _RM cells persist locally at sites of mucosal tissue, such as the lung, where they provide frontline defense against various pathogens. Importantly, however, T _RM cells are also involved in shaping the pathology of inflammatory diseases. A number of pioneering studies revealed important roles of CD8 ⁺ T _RM cells, particularly those in the local control of viral infection. However, the protective function and pathogenic role of CD4 ⁺ T _RM cells that reside within the mucosal tissue remain largely unknown. In this review, we discuss the ambivalent feature of CD4 ⁺ T _RM cells in the protective and pathological immune responses. We also review the transcriptional and epigenetic characteristics of CD4 ⁺ T _RM cells in the lung that have been elucidated by recent technical approaches. A better understanding of the function of CD4 ⁺ T _RM cells is crucial for the development of both effective vaccination against pathogens and new therapeutic strategies for intractable inflammatory diseases, such as inflammatory bowel diseases and chronic allergic diseases.