Abstract
Regulatory T cells, particularly their follicular resident subset, T-follicular regulatory cells, play a critical role in the maintenance of immune homeostasis and prevention of the expansion of T-follicular helper cells. One of the key mechanisms used by these cells is CTLA-4 dependent suppression of inflammation. In this chapter, we detail methods to increase the formation of T-follicular helper cells following vaccination by either depleting Treg cells, via Foxp3 linked diphtheria toxin receptor, or blocking CTLA-4 function by the use of antibodies.
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References
Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133(5):775–787. doi:10.1016/j.cell.2008.05.009
Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF, Srivastava M, Divekar DP, Beaton L, Hogan JJ, Fagarasan S, Liston A, Smith KG, Vinuesa CG (2011) Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med 17(8):975–982. doi:10.1038/nm.2425
Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S, Wang YH, Lim H, Reynolds JM, Zhou XH, Fan HM, Liu ZM, Neelapu SS, Dong C (2011) Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med 17(8):983–988. doi:10.1038/nm.2426
Wollenberg I, Agua-Doce A, Hernandez A, Almeida C, Oliveira VG, Faro J, Graca L (2011) Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol 187(9):4553–4560. doi:10.4049/jimmunol.1101328
Kim JM, Rasmussen JP, Rudensky AY (2007) Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8(2):191–197. doi:10.1038/ni1428
Kim J, Lahl K, Hori S, Loddenkemper C, Chaudhry A, deRoos P, Rudensky A, Sparwasser T (2009) Cutting edge: depletion of Foxp3+ cells leads to induction of autoimmunity by specific ablation of regulatory T cells in genetically targeted mice. J Immunol 183(12):7631–7634. doi:10.4049/jimmunol.0804308
Lahl K, Loddenkemper C, Drouin C, Freyer J, Arnason J, Eberl G, Hamann A, Wagner H, Huehn J, Sparwasser T (2007) Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 204(1):57–63. doi:10.1084/jem.20061852
Wing JB, Sakaguchi S (2014) Foxp3(+) T(reg) cells in humoral immunity. Int Immunol 26(2):61–69. doi:10.1093/intimm/dxt060
Wing JB, Ise W, Kurosaki T, Sakaguchi S (2014) Regulatory T cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the co-receptor CTLA-4. Immunity. doi:10.1016/j.immuni.2014.12.006
Buch T, Heppner FL, Tertilt C, Heinen TJ, Kremer M, Wunderlich FT, Jung S, Waisman A (2005) A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration. Nat Methods 2(6):419–426. doi:10.1038/nmeth762
Moon JJ, Chu HH, Hataye J, Pagan AJ, Pepper M, McLachlan JB, Zell T, Jenkins MK (2009) Tracking epitope-specific T cells. Nat Protoc 4(4):565–581. doi:10.1038/nprot.2009.9
Quezada SA, Peggs KS, Curran MA, Allison JP (2006) CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest 116(7):1935–1945. doi:10.1172/JCI27745
Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, Roddie C, Henry JY, Yagita H, Wolchok JD, Peggs KS, Ravetch JV, Allison JP, Quezada SA (2013) Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med 210(9):1695–1710. doi:10.1084/jem.20130579
Acknowledgements
We thank Yohko Kitagawa for helpful comments on the manuscript. J.B.W. is the recipient of a Japan Society for the Promotion of Science Young scientist B grant (25860356), S.S. is the recipient of Grants-in-Aid for Specially Promoted Research (20002007) and for Scientific Research (A) (26253030) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency.
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Wing, J.B., Sakaguchi, S. (2015). In Vivo Induction of T-Follicular Helper Cells by Modulation of Regulatory T Cell Function. In: Espéli, M., Linterman, M. (eds) T follicular Helper Cells. Methods in Molecular Biology, vol 1291. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2498-1_7
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DOI: https://doi.org/10.1007/978-1-4939-2498-1_7
Publisher Name: Humana Press, New York, NY
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