Biology:Tissue-resident memory T cell

From HandWiki
Jump to: navigation, search

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]

References

  1. "Tissue-resident memory T cells". Immunity 41 (6): 886–97. December 2014. doi:10.1016/j.immuni.2014.12.007. PMID 25526304. 
  2. "Tissue-resident memory T cells". Immunological Reviews 255 (1): 165–81. September 2013. doi:10.1111/imr.12087. PMID 23947354. 
  3. "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. September 2017. doi:10.1016/j.celrep.2017.08.078. PMID 28930685. 
  4. "Pathogenic role of tissue-resident memory T cells in autoimmune diseases". Autoimmunity Reviews 17 (9): 906–911. July 2018. doi:10.1016/j.autrev.2018.03.014. PMID 30005862. 
  5. "Formation and function of tissue-resident memory T cells during viral infection". Current Opinion in Virology 28: 61–67. February 2018. doi:10.1016/j.coviro.2017.11.001. PMID 29175730. 
  6. "The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin". Nature Immunology 14 (12): 1294–301. December 2013. doi:10.1038/ni.2744. PMID 24162776. 
  7. "Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues". Journal of Immunology 188 (10): 4866–75. May 2012. doi:10.4049/jimmunol.1200402. PMID 22504644. 
  8. "Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus". Nature Immunology 10 (5): 524–30. May 2009. doi:10.1038/ni.1718. PMID 19305395. 
  9. "Tissue-resident memory T cells". Immunological Reviews 255 (1): 165–81. September 2013. doi:10.1111/imr.12087. PMID 23947354. 
  10. "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. October 2010. doi:10.1073/pnas.1010201107. PMID 20923878. 
  11. "T cell memory. Skin-resident memory CD8⁺ T cells trigger a state of tissue-wide pathogen alert". Science 346 (6205): 101–5. October 2014. doi:10.1126/science.1254803. PMID 25278612. 
  12. "Resident memory T cells in human health and disease". Science Translational Medicine 7 (269): 269rv1. January 2015. doi:10.1126/scitranslmed.3010641. PMID 25568072.