Memory T cell

For other uses, see Memory cell (disambiguation).

A lymphocyte is shown in the center of this picture

1. After the naive T cell (N) encounters an antigen it becomes activated and begins to proliferate (divide) into many clones or daughter cells.
2. Some of the T cell clones will differentiate into effector T cells (E) that will perform the function of that cell (e.g. produce cytokines in the case of helper T cells or invoke cell killing in the case of cytotoxic T cells).
3. Some of the cells will form memory T cells (M) that will survive in an inactive state in the host for a long period of time until they re-encounter the same antigen and reactivate.

Memory T cells are a subset of infection- as well as potentially cancer-fighting T cells (also known as a T lymphocyte) that have previously encountered and responded to their cognate antigen; thus, the term antigen-experienced T cell is often applied. Such T cells can recognize foreign invaders, such as bacteria or viruses, as well as cancer cells. Memory T cells have become "experienced" by having encountered antigen during a prior infection, encounter with cancer, or previous vaccination. At a second encounter with the invader, memory T cells can reproduce to mount a faster and stronger immune response than the first time the immune system responded to the invader. This behaviour is utilized in T lymphocyte proliferation assays, which can reveal exposure to specific antigens.

Sub-populations

Within the overall memory T cell population, at least three distinct subpopulations have been described and can be recognised by the differential expression of chemokine receptor CCR7 and L-selectin (CD62L) ^[1].

• Central memory T_CM cells express L-selectin and the CCR7, they secrete IL-2, but not IFNγ or IL-4.

• Effector memory T_EM cells, however, do not express L-selectin or CCR7 but produce effector cytokines like IFNγ and IL-4.

More recently, other sub-populations have been explored using co-stimulatory molecules CD27 and CD28 expression in addition to CCR7 and CD62L ^[2].

Function

Antigen-specific memory T cells against viruses or other microbial molecules can be found in both T_CM and T_EM subsets. Although most information is currently based on observations in the cytotoxic T cells (CD8-positive) subset, similar populations appear to exist for both the helper T cells (CD4-positive) and the cytotoxic T cells.

• central memory (T_CM). The T_CM cells are thought to contain some properties associated with memory cells stem cells. T_CM display a capacity for self-renewal due to high levels of phosphorylation of an important transcription factor known as STAT5.^[3] In mice, T_CM cells have been shown to confer superior protection against viruses,^[4] bacteria,^[4] and cancer^[5] in several different model systems compared with T_EM cells.
• two highly related effector memory sub-types, which strongly express genes for molecules essential to the cytotoxic function of CD8 T cells:
  • effector memory (T_EM)
  • effector memory RA (T_EMRA)

• More recently, antigen-experienced CD8+ T cells with apparent self-renewal capabilities have been described in mice.^[6][7] This population, now termed stem cell memory (T_SCM), can be identified by the markers CD44(low)CD62L(high)CD122(high)sca-1(+) and are capable of generating T_CM and T_EM subsets while maintaining themselves. In preclinical studies, adoptively transferred T_SCM confer superior immunity compared with other T memory subsets.^[7] Whether such a population is found in humans is the subject of active investigation.

A recent study in Science found that T-cells in the spleen can synthesize acetylcholine in response to vagus nerve stimulation. (Science Sept 15, 2011. DOI : 10.1126/science.1209985) It is thought that this mechanism may play a role in down-regulating inflammation via TNF-alpha via macrophages.

See also

• Naive T cell
• V(D)J recombination of DNA
• Memory B cell

References

1. ^ Sallusto F, Langenkamp A, Geginat J, Lanzavecchia A (2000). "Functional subsets of memory T cells identified by CCR7 expression". Curr. Top. Microbiol. Immunol.. Current Topics in Microbiology and Immunology 251: 167–71. doi:10.1007/978-3-642-57276-0_21. ISBN 978-3-540-67569-3. PMID 11036772. 
2. ^ Okada R, Kondo T, Matsuki F, Takata H, Takiguchi M (September 2008). "Phenotypic classification of human CD4+ T cell subsets and their differentiation". Int. Immunol. 20 (9): 1189–1199. doi:10.1093/intimm/dxn075. PMID 18635582. 
3. ^ Willinger T, Freeman T, Hasegawa H, McMichael AJ, Callan MF (November 2005). "Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets". Journal of Immunology 175 (9): 5895–903. PMID 16237082. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16237082. 
4. ^ ^{a b} Wherry EJ, Teichgräber V, Becker TC et al. (March 2003). "Lineage relationship and protective immunity of memory CD8 T cell subsets". Nature Immunology 4 (3): 225–234. doi:10.1038/ni889. PMID 12563257. 
5. ^ Klebanoff CA, Gattinoni L, Torabi-Parizi P et al. (July 2005). "Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells". Proceedings of the National Academy of Sciences of the United States of America 102 (27): 9571–9576. doi:10.1073/pnas.0503726102. PMC 1172264. PMID 15980149. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1172264. 
6. ^ Zhang Y, Joe G, Hexner E, Zhu J, Emerson SG (December 2005). "Host-reactive CD8+ memory stem cells in graft-versus-host disease". Nature Medicine 11 (12): 1299–1305. doi:10.1038/nm1326. PMID 16288282. 
7. ^ ^{a b} Gattinoni L, Zhong XS, Palmer DC et al. (July 2009). "Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells". Nature Medicine 15 (7): 808–813. doi:10.1038/nm.1982. PMC 2707501. PMID 19525962. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2707501. 

Further reading

• Janeway, Charles (2005). Immunobiology: the immune system in health and disease. New York: Garland Science. ISBN 978-0-443-07310-6. 
• Lichtman, Andrew H.; Abbas, Abul K. (2003). Cellular and molecular immunology. Philadelphia: Saunders. ISBN 0-7216-0008-5. 

External links

• T-cell Group - Cardiff University