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      Tissue-Resident T Cells and Other Resident Leukocytes

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      Annual Review of Immunology

      Annual Reviews

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          Abstract

          Resident memory T (Trm) cells stably occupy tissues and cannot be sampled in superficial venous blood. Trm cells are heterogeneous but collectively constitute the most abundant memory T cell subset. Trm cells form an integral part of the immune sensing network, monitor for local perturbations in homeostasis throughout the body, participate in protection from infection and cancer, and likely promote autoimmunity, allergy, and inflammatory diseases and impede successful transplantation. Thus Trm cells are major candidates for therapeutic manipulation. Here we review CD8 + and CD4 + Trm ontogeny, maintenance, function, and distribution within lymphoid and nonlymphoid tissues and strategies for their study. We briefly discuss other resident leukocyte populations, including innate lymphoid cells, macrophages, natural killer and natural killer T cells, nonclassical T cells, and memory B cells. Lastly, we highlight major gaps in knowledge and propose ways in which a deeper understanding could result in new methods to prevent or treat diverse human diseases.

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          Most cited references 137

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          Two subsets of memory T lymphocytes with distinct homing potentials and effector functions.

          Naive T lymphocytes travel to T-cell areas of secondary lymphoid organs in search of antigen presented by dendritic cells. Once activated, they proliferate vigorously, generating effector cells that can migrate to B-cell areas or to inflamed tissues. A fraction of primed T lymphocytes persists as circulating memory cells that can confer protection and give, upon secondary challenge, a qualitatively different and quantitatively enhanced response. The nature of the cells that mediate the different facets of immunological memory remains unresolved. Here we show that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets. CCR7- memory cells express receptors for migration to inflamed tissues and display immediate effector function. In contrast, CCR7+ memory cells express lymph-node homing receptors and lack immediate effector function, but efficiently stimulate dendritic cells and differentiate into CCR7- effector cells upon secondary stimulation. The CCR7+ and CCR7- T cells, which we have named central memory (TCM) and effector memory (TEM), differentiate in a step-wise fashion from naive T cells, persist for years after immunization and allow a division of labour in the memory response.
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            Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm.

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              CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.

              The proper function of immune surveillance requires well-coordinated mechanisms in order to guide the patrolling immune cells through peripheral tissues and into secondary lymphoid organs. Analyzing gene-targeted mice, we identified the chemokine receptor CCR7 as an important organizer of the primary immune response. CCR7-deficient mice show severely delayed kinetics regarding the antibody response and lack contact sensitivity and delayed type hypersensitivity reactions. Due to the impaired migration of lymphocytes, these animals reveal profound morphological alterations in all secondary lymphoid organs. Upon activation, mature skin dendritic cells fail to migrate into the draining lymph nodes. Thus, in order to bring together lymphocytes and dendritic cells to form the characteristic microarchitecture of secondary lymphoid organs, CCR7 is required to rapidly initiate an adoptive immune response.
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                Author and article information

                Journal
                Annual Review of Immunology
                Annu. Rev. Immunol.
                Annual Reviews
                0732-0582
                1545-3278
                April 26 2019
                April 26 2019
                : 37
                : 1
                : 521-546
                Affiliations
                [1 ]Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota 55455, USA;,
                Article
                10.1146/annurev-immunol-042617-053214
                © 2019

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