Virtual memory T cell explained

Virtual memory T cells (T_VM) 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

T_VM 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 T_VM. 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. T_VM are cells specific and reactive to foreign antigens that have never met. There are different phenotypic mismatches between naive, true memory and T_VM. We can find functional differences after activation. It is easy to distinguish naive cells from memory, but true memory from T_VM can only be distinguished by CD49d and CD122 markers.^[5]

T_VM produce a stronger inflammatory response using IL-12 and IL-18 cytokines than naive T cells.^[6] They are a significant producer of IFN-γ.^[7] Compared to other naive phenotypes, T_VM 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.

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.

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.

CD4 positive T_VM

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.

Notes and References

1. Haluszczak C, Akue AD, Hamilton SE, Johnson LD, Pujanauski L, Teodorovic L, Jameson SC, Kedl RM . 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 . February 2009 . 19188498 . 2646575 . 10.1084/jem.20081829 .
2. White JT, Cross EW, Burchill MA, Danhorn T, McCarter MD, Rosen HR, O'Connor B, Kedl RM . Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner . Nature Communications . 7 . 1 . 11291 . April 2016 . 27097762 . 4844673 . 10.1038/ncomms11291 . 2016NatCo...711291W .
3. Akue AD, Lee JY, Jameson SC . Derivation and maintenance of virtual memory CD8 T cells . Journal of Immunology . 188 . 6 . 2516–23 . March 2012 . 22308307 . 3294185 . 10.4049/jimmunol.1102213 .
4. Sosinowski T, White JT, Cross EW, Haluszczak C, Marrack P, Gapin L, Kedl RM . 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 . March 2013 . 23355737 . 3578102 . 10.4049/jimmunol.1203149 .
5. Drobek A, Moudra A, Mueller D, Huranova M, Horkova V, Pribikova M, Ivanek R, Oberle S, Zehn D, McCoy KD, Draber P, Stepanek O . Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells . The EMBO Journal . 37 . 14 . e98518 . July 2018 . 29752423 . 6043851 . 10.15252/embj.201798518 .
6. White JT, Cross EW, Kedl RM . + T cells: where they come from and why we need them . Nature Reviews. Immunology . 17 . 6 . 391–400 . June 2017 . 28480897 . 5569888 . 10.1038/nri.2017.34 .
7. Lee JY, Hamilton SE, Akue AD, Hogquist KA, Jameson SC . 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 . August 2013 . 23898211 . 3746847 . 10.1073/pnas.1307572110 . 2013PNAS..11013498L . free .
8. 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 . + 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 . February 2017 . 27894837 . 6066671 . 10.1016/j.jaut.2016.11.001 .