Tissue-resident memory T cell

Tissue-resident memory T cells or TRM cells represent a lineage of T cells that occupies tissues (skin, lung, gastrointestinal tract, etc.) without recirculating. TRM cells are transcriptionally, phenotypically and functionally distinct from central memory and effector memory T cells which recirculate between blood, the T cell zones of secondary lymphoid organs, lymph and nonlymphoid tissues. The role of TRM cells is provide superior protection against infection in extralymphoid tissues.[1][2]

Phenotype

The main cell surface markers that has been associated with TRM in human tissues are CD69 and CD103. CD103 is expressed by most CD8+ TRM cells and rarely by CD4+ TRM cells. CD69 has key role in distinguishing T cells in tissues from those in circulation. However, expression levels can differ between T cells in different tissues.[3] Another marker that can be used to separate two TRM cell subsets with distinct functions is CD49a. CD8+ CD49a+ TRM cells produce perforin and IFN-gamma, which is a key cytokine in clearing virus infections. CD8+ CD49a- TRM cells produce IL-17.[4]

Development

TRM cells develop from circulating effector memory T cell precursors in response to antigen. The main role in formation of TRM cells has CD103 and expression of this integrin is dependent on the cytokine TGFβ. CD8+ effector T cells that lack TGFβ fail to upregulate CD103, and subsequently do not differentiate into TRM cells. The important role in development of TRM cells have various cytokines that support TRM cell formation and survival. For example, homeostatic cytokine IL-15, pro-inflammatory cytokines such as IL-12 and IL-18, and barrier cytokines such as IL-33.[5][6][7]

Function

TRM cells reside in many tissues that create barriers against outside environment and thus provide defense against incoming pathogens. In the skin, lung, brain, and vagina TRM cells are required to provide rapid control of infection and are more efficient than effector memory T cells. TRM cells also express granzyme B which help limit the spread of pathogens at the site of infection. TRM cells are able to activate innate and adaptive leukocytes to protect the host.[8][9][10][11]

Role in disease pathogenesis

Autoreactive TRM cells may induce some autoimmune disorders, such as multiple sclerosis, lupus nephritis, rheumatoid arthritis, autoimmune hepatitis or psoriasis.[12]

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References
  1. Schenkel JM, Masopust D (December 2014). "Tissue-resident memory T cells". Immunity. 41 (6): 886–97. doi:10.1016/j.immuni.2014.12.007. PMC 4276131. PMID 25526304.
  2. Shin H, Iwasaki A (September 2013). "Tissue-resident memory T cells". Immunological Reviews. 255 (1): 165–81. doi:10.1111/imr.12087. PMC 3748618. PMID 23947354.
  3. Kumar BV, Ma W, Miron M, Granot T, Guyer RS, Carpenter DJ, et al. (September 2017). "Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites". Cell Reports. 20 (12): 2921–2934. doi:10.1016/j.celrep.2017.08.078. PMC 5646692. PMID 28930685.
  4. Wu H, Liao W, Li Q, Long H, Yin H, Zhao M, Chan V, Lau CS, Lu Q (July 2018). "Pathogenic role of tissue-resident memory T cells in autoimmune diseases". Autoimmunity Reviews. 17 (9): 906–911. doi:10.1016/j.autrev.2018.03.014. PMID 30005862.
  5. Shin H (February 2018). "Formation and function of tissue-resident memory T cells during viral infection". Current Opinion in Virology. 28: 61–67. doi:10.1016/j.coviro.2017.11.001. PMID 29175730.
  6. Mackay LK, Rahimpour A, Ma JZ, Collins N, Stock AT, Hafon ML, et al. (December 2013). "The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin". Nature Immunology. 14 (12): 1294–301. doi:10.1038/ni.2744. hdl:1885/12900. PMID 24162776.
  7. Casey KA, Fraser KA, Schenkel JM, Moran A, Abt MC, Beura LK, et al. (May 2012). "Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues". Journal of Immunology. 188 (10): 4866–75. doi:10.4049/jimmunol.1200402. PMC 3345065. PMID 22504644.
  8. Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR (May 2009). "Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus". Nature Immunology. 10 (5): 524–30. doi:10.1038/ni.1718. PMID 19305395.
  9. Shin H, Iwasaki A (September 2013). "Tissue-resident memory T cells". Immunological Reviews. 255 (1): 165–81. doi:10.1111/imr.12087. PMC 3748618. PMID 23947354.
  10. Wakim LM, Woodward-Davis A, Bevan MJ (October 2010). "Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence". Proceedings of the National Academy of Sciences of the United States of America. 107 (42): 17872–9. doi:10.1073/pnas.1010201107. PMC 2964240. PMID 20923878.
  11. Ariotti S, Hogenbirk MA, Dijkgraaf FE, Visser LL, Hoekstra ME, Song JY, et al. (October 2014). "T cell memory. Skin-resident memory CD8⁺ T cells trigger a state of tissue-wide pathogen alert". Science. 346 (6205): 101–5. doi:10.1126/science.1254803. PMID 25278612.
  12. Clark RA (January 2015). "Resident memory T cells in human health and disease". Science Translational Medicine. 7 (269): 269rv1. doi:10.1126/scitranslmed.3010641. PMC 4425129. PMID 25568072.
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