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I M M U N O L O G I C A L M E M O R Y R E V I E W
I M M U N O L O G I C A L M E M O R Y R E V I E W
Regional and mucosal memory T cells
2011Nature America, Inc. All rights reserved.
Brian S Sheridan & Leo Lefranois
After infection, most antigen-specific memory T cells reside in nonlymphoid tissues. Tissue-specific programming during priming leads to directed migration of T cells to the appropriate tissue, which promotes the development of tissue-resident memory in organs such as intestinal mucosa and skin. Mechanisms that regulate the retention of tissue-resident memory T cells include transforming growth factor-b (TGF-b)-mediated induction of the E-cadherin receptor CD103 and downregulation of the chemokine receptor CCR7. These pathways enhance protection in internal organs, such as the nervous system, and in the barrier tissuesthe mucosa and skin. Memory T cells that reside at these surfaces provide a first line of defense against subsequent infection, and defining the factors that regulate their development is critical to understanding organ-based immunity.
The development and functional programming of the immune system is characterized by regionalization at multiple levels. For example, the generation of mature CD4+ and CD8+ T cells is compartmentalized in the thymus and follows a prescribed set of selection steps geared toward achieving a functionally responsive and minimally autoreactive peripheral repertoire1. Although certain stochastic events designate outcomes in this process, the system is essentially closed and under normal circumstances is not heavily influenced by extrathymic events. In contrast, mature T cells responding to antigens are considerably affected by the context in which antigen presentation occurs, which often represents a continuously changing environment. Thus, the immune response to infection is subjected to a dynamic process with active changes to cell types and their locations, concentrations of inflammatory and anti-inflammatory mediators, blood and lymph flow, and antigen concentrations. In the secondary lymphoid tissues, where T cell priming occurs, the sum of these alterations dictates the type of effector T cells generated and the nature of the memory populations produced.
Memory T cells are characterized by considerable heterogeneity at the phenotypic and functional levels. Early studies identified functionally distinct subsets...