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      Tissue-resident memory T cells: local specialists in immune defence.

      Author(s): 1 , 2 , 1 , 2
      Publication date (Electronic):
      Journal: Nature reviews. Immunology

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          Abstract

          T cells have crucial roles in protection against infection and cancer. Although the trafficking of memory T cells around the body is integral to their capacity to provide immune protection, studies have shown that specialization of some memory T cells into unique tissue-resident subsets gives the host enhanced regional immunity. In recent years, there has been considerable progress in our understanding of tissue-resident T cell development and function, revealing mechanisms for enhanced protective immunity that have the potential to influence rational vaccine design. This Review discusses the major advances and the emerging concepts in this field, summarizes what is known about the differentiation and the protective functions of tissue-resident memory T cells in different tissues in the body and highlights key unanswered questions.

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          Lineage relationship and protective immunity of memory CD8 T cell subsets.

          E. John Wherry, Volker Teichgräber, Todd C. Becker … (2003)
          Memory CD8 T cells can be divided into two subsets, central (T(CM)) and effector (T(EM)), but their lineage relationships and their ability to persist and confer protective immunity are not well understood. Our results show that T(CM) have a greater capacity than T(EM) to persist in vivo and are more efficient in mediating protective immunity because of their increased proliferative potential. We also demonstrate that, following antigen clearance, T(EM) convert to T(CM) and that the duration of this differentiation is programmed within the first week after immunization. We propose that T(CM) and T(EM) do not necessarily represent distinct subsets, but are part of a continuum in a linear naive --> effector --> T(EM) --> T(CM) differentiation pathway.
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            Commensal-dendritic-cell interaction specifies a unique protective skin immune signature.

            Shruti Naik, Nicolas Bouladoux, Jonathan Linehan … (2015)
            The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.
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              Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection.

              John Teijaro, Damian Turner, Quynh Pham … (2011)
              We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab labeling, and expressed elevated levels of CD69 and CD11a compared with those of circulating memory populations. Importantly, influenza-specific lung-resident memory CD4 T cells served as in situ protectors to respiratory viral challenge, mediating enhanced viral clearance and survival to lethal influenza infection. By contrast, memory CD4 T cells isolated from spleen recirculated among multiple tissues without retention and failed to mediate protection to influenza infection, despite their ability to expand and migrate to the lung. Our results reveal tissue compartmentalization as a major determining factor for immune-mediated protection in a key mucosal site, important for targeting local protective responses in vaccines and immunotherapies.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Nat. Rev. Immunol.
                Title: Nature reviews. Immunology
                ISSN (Electronic): 1474-1741
                ISSN (Print): 1474-1733
                Publication date (Electronic): Feb 2016
                Volume: 16
                Issue: 2
                Affiliations
                [1 ] Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
                [2 ] The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Victoria 3000, Australia.
                Article
                Publisher Item ID: nri.2015.3
                DOI: 10.1038/nri.2015.3
                PubMed ID: 26688350
                SO-VID: bb18f256-4084-48d1-be22-a48743f1bcf3
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