THE PREDOMINANT ROLE OF CD4+T CELL-DERIVED SMALL EXTRACELLULAR VESICLES IN IMMUNE ENHANCEMENT

Main Article Content

Jiayi Gong
Nawab Ali
Muhammad Abubakar
Ashfaq Ahmad Shah Bukhari
Muhammad Ilyas
Ujala Bashir
Majid Ali
Muhammad Haidar Zaman

Keywords

Small Extracellular Vesicles (sEV), Lymphocytes, T Cell, B Cell, Immune Enhancement

Abstract

Background: The human lymphocyte population provides adaptive and humoral immunity; however, the defending function and activities of lymphocytes were found abridged in many infections. Research has also proved the lack of CD4+ T cells in these infections. Thus, this study was conducted to investigate the role of small extracellular vesicles (sEV) derived from CD4+ T cells in immune enhancement.
Methodology: CD4+ T cells were activated, and sEV was Isolated and identified. Using different immunological techniques, including Flow cytometry, ELISA, Western Blotting, and immunofluorescence, the endorsement of activation, proliferation, and antibody production by lymphocytes was observed.
Result and discussion: The sEV derived from CD4+ T cells have expressed CD4, CD25, and ICOS molecules connected the biological properties of sEV to the parent cells. The result indicates that CD86 and MHCII expressions on the B cell surface were enhanced in the derived sEV-treated group, conforming that CD4+ T cell-derived sEV can promote B cell activation. In addition, the B cells treated with CD4+ T cell-derived sEV have greater CFSE and SSC-Height subsets and prove they can promote B cell proliferation. Furthermore, The IgG level in cells (wells) treated with 50μg CD4+ T cell-derived sEV was four times higher, corroborating its ability to promote antibody production of B cells.
Conclusion: sEV derived from CD4+ T cells enhances immune responses by promoting activation, proliferation, and IgG production by B cells.

Abstract 171 | PDF Downloads 51

References

1. Pan, L., et al., A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations. Hum Mol Genet, 2014. 23(8): p. 2210-9.
2. Vora, K.A., K. Tumas-Brundage, and T. Manser, Contrasting the In Situ Behavior of a Memory B Cell Clone During Primary and Secondary Immune Responses. The Journal of Immunology, 1999. 163(8): p. 4315.
3. Luckheeram, R.V., et al., CD4⁺T cells: differentiation and functions. Clin Dev Immunol, 2012. 2012: p. 925135.
4. van den Berg, R., I. van Hoogstraten, and M. van Agtmael, Non-responsiveness to hepatitis B vaccination in HIV seropositive patients; possible causes and solutions. AIDS Rev, 2009. 11(3): p. 157-64.
5. Eleftheriadis, T., et al., Disturbances of acquired immunity in hemodialysis patients. Semin Dial, 2007. 20(5): p. 440-51.
6. Saco, T.V., A.T. Strauss, and D.K. Ledford, Hepatitis B vaccine nonresponders: Possible mechanisms and solutions. Ann Allergy Asthma Immunol, 2018. 121(3): p. 320-327.
7. Sempere, L., et al., Factors predicting response to hepatitis B vaccination in patients with inflammatory bowel disease. Vaccine, 2013. 31(30): p. 3065-71.
8. Rosenberg, C., et al., Age is an important determinant in humoral and T cell responses to immunization with hepatitis B surface antigen. Hum Vaccin Immunother, 2013. 9(7): p. 1466-76.
9. Der, J.E., et al., A murine monoclonal antibody, MoAb HMSA-5, against a melanosomal component highly expressed in early stages, and common to normal and neoplastic melanocytes. Br J Cancer, 1993. 67(1): p. 47-57.
10. Abrahams, V.M., et al., First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod, 2004. 10(1): p. 55-63.
11. van Niel, G., et al., Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology, 2001. 121(2): p. 337-49.
12. Raposo, G., et al., B lymphocytes secrete antigen-presenting vesicles. J Exp Med, 1996. 183(3): p. 1161-72.
13. Blanchard, N., et al., TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol, 2002. 168(7): p. 3235-41.
14. Yáñez-Mó, M., et al., Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles, 2015. 4: p. 27066.
15. Mathivanan, S. and R.J. Simpson, ExoCarta: A compendium of exosomal proteins and RNA. Proteomics, 2009. 9(21): p. 4997-5000.
16. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol, 2007. 9(6): p. 654-9.
17. Batrakova, E.V. and M.S. Kim, Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release, 2015. 219: p. 396-405.
18. Théry, C., et al., Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol, 2002. 3(12): p. 1156-62.
19. Mittelbrunn, M., et al., Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun, 2011. 2: p. 282.
20. Mittelbrunn, M. and F. Sánchez-Madrid, Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol, 2012. 13(5): p. 328-35.
21. Cheng, L., Y. Wang, and L. Huang, Exosomes from M1-Polarized Macrophages Potentiate the Cancer Vaccine by Creating a Pro-inflammatory Microenvironment in the Lymph Node. Mol Ther, 2017. 25(7): p. 1665-1675.
22. Acevedo, R., et al., Bacterial outer membrane vesicles and vaccine applications. Front Immunol, 2014. 5: p. 121.
23. Atayde, V.D., et al., Exploitation of the Leishmania exosomal pathway by Leishmania RNA virus 1. Nat Microbiol, 2019. 4(4): p. 714-723.
24. Atayde, V.D., et al., Exosome Secretion by the Parasitic Protozoan Leishmania within the Sand Fly Midgut. Cell Rep, 2015. 13(5): p. 957-67.

Most read articles by the same author(s)