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Regulatory T Cells

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Basics of Hematopoietic Stem Cell Transplant

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Abstract

Regulatory T cells (T regs) are a subtype to T cells that work to inhibit the immune response of other T cells. Their main function is to maintain homeostasis and mediate self-tolerance. They play a major role in preventing autoimmunity by inhibiting T cell proliferation and cytokine production. T regs also dampen the killer T cell response once the infection has been dealt with, so as to protect the normal tissue. T regs can also prevent and treat graft versus host disease (GVHD). Failure of T reg function leads to increased self-tissue injury as cytotoxic response of T cells will go uncontrolled. Increased activity of T regs can lead to increased risk of infections, and cancers by suppressing tumor-specific T cell immunity. T regs play a crucial role in establishment of tolerance after allogeneic stem cell transplant.

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References

  1. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61.

    Article  CAS  PubMed  Google Scholar 

  2. Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, et al. Hassall’s corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature. 2005;436(7054):1181–5.

    Article  CAS  PubMed  Google Scholar 

  3. Jordan MS, Boesteanu A, Reed AJ, Petrone AL, Holenbeck AE, Lerman MA, et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol. 2001;2(4):301–6.

    Article  CAS  PubMed  Google Scholar 

  4. Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF. Cutting edge: TGF-β induces a regulatory phenotype in CD4+CD25− T cells through Foxp3 induction and Down-regulation of Smad7. J Immunol. 2004;172(9):5149–53.

    Article  CAS  PubMed  Google Scholar 

  5. Cobbold SP, Castejon R, Adams E, Zelenika D, Graca L, Humm S, et al. Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J Immunol. 2004;172(10):6003–10.

    Article  CAS  PubMed  Google Scholar 

  6. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses? Int Immunol. 2009;21(10):1105–11.

    Article  CAS  PubMed  Google Scholar 

  7. Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27(4):635–46.

    Article  CAS  PubMed  Google Scholar 

  8. Burchill MA, Yang J, Vang KB, Farrar MA. Interleukin-2 receptor signaling in regulatory T cell development and homeostasis. Immunol Lett. 2007;114(1):1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Arce-Sillas A, Álvarez-Luquín DD, Tamaya-Domínguez B, Gomez-Fuentes S, Trejo-García A, Melo-Salas M, et al. Regulatory T cells: molecular actions on effector cells in immune regulation. J Immunol Res. 2016;2016:1720827.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mucida D, Park Y, Cheroutre H. From the diet to the nucleus: vitamin a and TGF-β join efforts at the mucosal interface of the intestine. Semin Immunol. 2009;21(1):14–21.

    Article  CAS  PubMed  Google Scholar 

  11. Campbell C, Dikiy S, Bhattarai SK, Chinen T, Matheis F, Calafiore M, et al. Extrathymically generated regulatory T cells establish a niche for intestinal border-dwelling bacteria and affect physiologic metabolite balance. Immunity. 2018;48(6):1245–1257.e9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med. 2007;204(8):1775–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Belkaid Y, Harrison OJ. Homeostatic immunity and the microbiota. Immunity. 2017;46(4):562–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nguyen VH, Zeiser R, daSilva DL, Chang DS, Beilhack A, Contag CH, et al. In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation. Blood. 2007;109(6):2649–56.

    Article  CAS  PubMed  Google Scholar 

  15. Rieger K, Loddenkemper C, Maul J, Fietz T, Wolff D, Terpe H, et al. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood. 2006;107(4):1717–23.

    Article  CAS  PubMed  Google Scholar 

  16. Engelhardt BG, Sengsayadeth SM, Jagasia M, Savani BN, Kassim AA, Lu P, et al. Tissue-specific regulatory T cells: biomarker for acute graft-vs-host disease and survival. Exp Hematol. 2012;40(12):974–982.e1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Elias S, Rudensky AY. Therapeutic use of regulatory T cells for graft-versus-host disease. Br J Haematol. 2019;187(1):25–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shin HJ, Baker J, Leveson-Gower DB, Smith AT, Sega EI, Negrin RS. Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells. Blood. 2011;118(8):2342–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gatza E, Rogers CE, Clouthier SG, Lowler KP, Tawara I, Liu C, et al. Extracorporeal photopheresis reverses experimental graft-versus-host disease through regulatory T cells. Blood. 2008;112(4):1515–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Riegel C, Boeld TJ, Doser K, Huber E, Hoffmann P, Edinger M. Efficient treatment of murine acute GvHD by in vitro expanded donor regulatory T cells. Leukemia. 2020;34(3):895–908.

    Article  CAS  PubMed  Google Scholar 

  21. Chatila TA. Role of regulatory T cells in human diseases. J Allergy Clin Immunol. 2005;116(5):949–59. quiz 960

    Article  CAS  PubMed  Google Scholar 

  22. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27(1):20–1.

    Article  CAS  PubMed  Google Scholar 

  23. Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest. 2000;106(12):R75–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Furukawa A, Wisel SA, Tang Q. Impact of immune-modulatory drugs on regulatory T cell. Transplantation. 2016;100(11):2288–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Libert C, Dejager L. How steroids steer T cells. Cell Rep. 2014;7(4):938–9.

    Article  CAS  PubMed  Google Scholar 

  26. Mathian A, Jouenne R, Chader D, Cohen-Aubart F, Haroche J, Fadlallah J, et al. Regulatory T cell responses to high-dose methylprednisolone in active systemic lupus erythematosus. PLoS One. 2015;10(12):e0143689. [cited 2021 Jan 10]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667921/.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Feng X, Kajigaya S, Solomou EE, Keyvanfar K, Xu X, Raghavachari N, et al. Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood. 2008;111(7):3675–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dekker L, de Koning C, Lindemans C, Nierkens S. Reconstitution of T cell subsets following allogeneic hematopoietic cell transplantation. Cancers. 2020;12(7):1974. Jul 20 [cited 2020 Sep 8]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409323/.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Hemato-oncology and Bone Marrow Transplantation, Venkateshwar Hospital, New Delhi, Delhi, India

    Sanjeev Kumar Sharma

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  1. Sanjeev Kumar Sharma
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© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

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Sharma, S.K. (2023). Regulatory T Cells. In: Basics of Hematopoietic Stem Cell Transplant. Springer, Singapore. https://doi.org/10.1007/978-981-19-5802-1_8

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  • DOI: https://doi.org/10.1007/978-981-19-5802-1_8

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-19-5801-4

  • Online ISBN: 978-981-19-5802-1

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