Review Article | Published:

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

Nature Reviews Immunology volume 16, pages 7989 (2016) | Download Citation

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.

Key points

  • Tissue-resident CD4+ and CD8+ T cells have been identified in many tissues and organs of mice and humans. These cells are defined as those that undergo little or no recirculation.

  • Tissue residency is not just a feature of subsets of memory αβ T cells. Other populations of immune cells, including regulatory T cells, natural killer T (NKT) cells, NK cells, γδ T cells and innate lymphoid cells have been defined as being permanently resident in tissues.

  • Expression of CD69 and the integrin CD103 were originally defined as key markers of tissue-resident memory T cells (TRM cells). However, expression levels can differ between T cells in different tissues and TRM cells lacking both of these markers have now been described.

  • TRM cell development involves several checkpoints, including tissue entry, local retention and subsequent responsiveness to local cytokines that support TRM cell formation and survival.

  • TRM cells are crucial for local immunity and recall responses. New generation vaccines should be designed to induce both TRM cells and circulating memory T cells for optimal protection against infection.

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Acknowledgements

S.N.M. and L.K.M. are supported by grants from the Australian Research Council and from the National Health and Medical Research Council of Australia.

Author information

Affiliations

  1. Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.

    • Scott N. Mueller
    •  & Laura K. Mackay
  2. The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Victoria 3000, Australia.

    • Scott N. Mueller
    •  & Laura K. Mackay

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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Scott N. Mueller or Laura K. Mackay.

Glossary

Immunosurveillance

The monitoring process of the immune system that detects foreign pathogens or abnormal cells in the body.

Immunological memory

The capacity of the immune system to respond more rapidly and more effectively to foreign antigen upon re-encounter.

Effector memory T cells

(TEM cells). A subset of memory T cells that lack expression of the secondary lymphoid homing molecules L-selectin and CC-chemokine receptor 7 (CCR7) and that can be found in non-lymphoid tissues. These memory T cells can exert immediate effector functions and produce cytokines including interferon-γ.

Central memory T cell

(TCM cell). A type of memory T cell that expresses L-selectin and CC-chemokine receptor 7 (CCR7) and that can recirculate through secondary lymphoid organs. TCM cells can produce interleukin-2 and can proliferate extensively in response to restimulation.

Parenchyma

The functional tissue of an organ, supported by the stroma.

Fixed drug eruptions

Allergic reactions that recur at the same site on the skin following each exposure to a particular drug. Exposure to the drug may occur systemically but results in localized lesions.

Mammalian target of rapamycin pathway

(mTOR pathway). mTOR protein is activated by T cell receptor signalling and cytokines, and can regulate cell proliferation, survival, transcription and protein synthesis.

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DOI

https://doi.org/10.1038/nri.2015.3

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