Virtual memory T cells (TVM) are a subtype of T lymphocytes. These are cells that have a memory phenotype but have not been exposed to a foreign antigen. They are classified as memory cells but do not have an obvious memory function. They were first observed and described in 2009.[1] The name comes from a computerized "virtual memory" that describes a working memory based on an alternative use of an existing space.

Origin

TVM arise from autoreactive T cells during the thymus section. Autoreactive lymphocytes are commonly removed in the thymus because they recognize the body's own structure and could induce autoimmune disease. However, some autoreactive CD8+ T cells are intended for development into TVM. This process is controlled by CD8-Lck. The generation and maintenance of the TVM population depends on the transcription factors Eomes and IRF4, type I interfering signaling. The presence of the IL-15 cytokine is then essential.[2][3][4]

Function

The existence of memory T cells is also known in non-immunized animals. TVM are cells specific and reactive to foreign antigens that have never met. There are different phenotypic mismatches between naive, true memory and TVM. We can find functional differences after activation. It is easy to distinguish naive cells from memory, but true memory from TVM can only be distinguished by CD49d and CD122 markers.[1][5]

TVM produce a stronger inflammatory response using IL-12 and IL-18 cytokines than naive T cells.[1][6][3] They are a significant producer of IFN-γ.[7] Compared to other naive phenotypes, TVM represents only 10—30% of the population, but outperforms other types of subpopulation with its stronger proliferation. However, the reaction is slower than true memory cells. These properties suggest that virtual memory T cells may participate in both innate and adaptive immune responses during the immune response.[1]

Another indispensable feature is the suppression of potential states. This occurs already in the development of virtual memory cells from autoreactive T cell clones. For this reason, some scientists thought that TVM could be used in the fight against autoimmunity, but so far no evidence has been found.[5]

The physiological role of virtual memory T lymphocytes has yet to be investigated, but research suggests that they have a unique type of response to pathogens and contribute to the functional diversity of the T cell immune system, which is required for effective immune defense.[2][3]

CD4 positive TVM

Previous paragraphs dealt with only CD8+ T lymphocytes, but CD4+ virtual memory T cells are also described.[8] The function of these cells is not known, but an even more likely relationship to autoimmune conditions is assumed, whether in their suppression or formation.[8]

References

  1. 1 2 3 4 Haluszczak C, Akue AD, Hamilton SE, Johnson LD, Pujanauski L, Teodorovic L, Jameson SC, Kedl RM (February 2009). "The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion". The Journal of Experimental Medicine. 206 (2): 435–48. doi:10.1084/jem.20081829. PMC 2646575. PMID 19188498.
  2. 1 2 White JT, Cross EW, Burchill MA, Danhorn T, McCarter MD, Rosen HR, O'Connor B, Kedl RM (April 2016). "Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner". Nature Communications. 7 (1): 11291. Bibcode:2016NatCo...711291W. doi:10.1038/ncomms11291. PMC 4844673. PMID 27097762.
  3. 1 2 3 Akue AD, Lee JY, Jameson SC (March 2012). "Derivation and maintenance of virtual memory CD8 T cells". Journal of Immunology. 188 (6): 2516–23. doi:10.4049/jimmunol.1102213. PMC 3294185. PMID 22308307.
  4. ↑ Sosinowski T, White JT, Cross EW, Haluszczak C, Marrack P, Gapin L, Kedl RM (March 2013). "CD8α+ dendritic cell trans presentation of IL-15 to naive CD8+ T cells produces antigen-inexperienced T cells in the periphery with memory phenotype and function". Journal of Immunology. 190 (5): 1936–47. doi:10.4049/jimmunol.1203149. PMC 3578102. PMID 23355737.
  5. 1 2 Drobek A, Moudra A, Mueller D, Huranova M, Horkova V, Pribikova M, Ivanek R, Oberle S, Zehn D, McCoy KD, Draber P, Stepanek O (July 2018). "Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells". The EMBO Journal. 37 (14): e98518. doi:10.15252/embj.201798518. PMC 6043851. PMID 29752423.
  6. ↑ White JT, Cross EW, Kedl RM (June 2017). "+ T cells: where they come from and why we need them". Nature Reviews. Immunology. 17 (6): 391–400. doi:10.1038/nri.2017.34. PMC 5569888. PMID 28480897.
  7. ↑ Lee JY, Hamilton SE, Akue AD, Hogquist KA, Jameson SC (August 2013). "Virtual memory CD8 T cells display unique functional properties". Proceedings of the National Academy of Sciences of the United States of America. 110 (33): 13498–503. Bibcode:2013PNAS..11013498L. doi:10.1073/pnas.1307572110. PMC 3746847. PMID 23898211.
  8. 1 2 Marusina AI, Ono Y, Merleev AA, Shimoda M, Ogawa H, Wang EA, Kondo K, Olney L, Luxardi G, Miyamura Y, Yilma TD, Villalobos IB, Bergstrom JW, Kronenberg DG, Soulika AM, Adamopoulos IE, Maverakis E (February 2017). "+ virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity". Journal of Autoimmunity. 77: 76–88. doi:10.1016/j.jaut.2016.11.001. PMC 6066671. PMID 27894837.
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