Resident Memory T Cells (TRM) Are Abundant in Human Lung: Diversity, Function, and Antigen Specificity

Recent studies have shown that tissue resident memory T cells (T-RM) are critical to antiviral host defense in peripheral tissues. This new appreciation of T-RM that reside in epithelial tissues and mediate host defense has been studied most extensively in skin: adult human skin contains large numbers of functional T-RM that express skin specific markers. Indeed, more than twice as many T cells reside in skin as in peripheral blood. This T cell population has a diverse T cell receptor repertoire, and can produce a broad array of cytokines. More recently, we have begun to examine other epithelial tissues for the presence of resident T cells. In the present study, we asked whether analogous populations of resident T cells could be found in human lung. We were able to demonstrate abundant resident T cells in human lung-more than 10 billion T cells were present. Lung T cells were largely of the effector memory T cell (T-EM) phenotype, though small numbers of central memory T cells (T-CM) and T regulatory cells (T-reg) could be identified. Lung T cells had a diverse T cell receptor repertoire and subsets produced IL-17, IL-4, IFN gamma, as well as TNF alpha. A significant number of lung T-RM CD4+ Th cells produced more than one cytokine, identifying them as "multifunctional'' Th1 type cells. Finally, lung T-RM, but not T-RM resident to skin or T cells from blood, proliferated in response to influenza virus. This work suggests that normal human lung contains large numbers of T-RM cells, and these cells are poised to respond to recall antigens previously encountered through lung mucosa. This population of T cells may contribute to the pathogenesis of asthma and other T cell mediated lung diseases.