Behavior and function of virus-specific tissue-resident memory T cells

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Memory T cells are the progeny of naive antigen-specific T cells that have been clonally expanded in the course of a primary response and that survived once the antigen has been eliminated. They have been broadly divided into two main subsets termed central and effector memory T cells. Central memory T cells localize in secondary lymphoid tissues, show high proliferative potential but limited effector function whereas effector memory T cells migrate through non-lymphoid peripheral tissues, produce rapidly effector cytokines but exhibit limited proliferation capacity. In the past few years, a new type of memory T cells has been identified in the skin epidermis, the brain, the intestinal epithelium and the respiratory mucosa. These T cells do not exit their home tissues in the resting host and have therefore been termed tissue-resident memory T cells. They may represent a first line of defense against pathogens that target these tissues.We recently discovered a unique population of antigen-specific memory CD8 T cells in the salivary glands of virus-immune mice that exhibit anti-viral activity and that might be considered as tissue-resident memory T cells. Furthermore, these T cells expressed the epithelial adhesion molecule E-cadherin which promoted their accumulation in this tissue. In the first part of this project, we will investigate the mechanisms of tissue accumulation, anatomical localization and homeostatic regulation of this fascinating cell population. Interestingly, we already observed that memory CD8 T cells in the salivary glands show an intraepithelial localization similar to lymphocytes in the gut mucosa. In ongoing experiments, we further identified a population of virus-specific CD8 T cells in the thymus of virus-immune mice that also express markers characteristic of tissue-resident memory T cells. In the second part of this project, we will find out whether these thymic memory T cells are indeed tissue-resident and able to exert anti-viral activity. In addition, we will determine whether local antigen is required for the generation of such thymic memory T cells that localize as cell clusters in the thymic medulla and as single cells in the cortex. The thymus is a well-known primary lymphoid organ for the generation of naïve T cells and thus, the notion that it may also serve as a site for tissue-resident memory T cells is very intriguing.