Abstract
In vitro strategies to obtain different T helper cell subsets from naïve precursors are usually characterized by anti-CD3 plus anti-CD28 monoclonal antibody stimulation of naïve CD4+ T cells (derived from both peripheral blood or umbilical cord blood) in the presence of specific polarizing cytokines. In this chapter, we describe detailed protocols to obtain in vitro differentiation of human naïve CD4+ T cells into Th1, Th2, or Th17 cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173
Romagnani S (1994) Lymphokine production by human T cells in disease states. Annu Rev Immunol 12:227–257
Harrington LE, Hatton RD, Mangan PR et al (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6(11):1123–1132
Annunziato F, Cosmi L, Santarlasci V et al (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204(8):1849–1861
Hsieh CS, Macatonia SE, Tripp CS et al (1993) Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260(5107):547–549
Szabo SJ, Sullivan BM, Peng SL et al (2003) Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 21:713–758
Le Gros G, Ben-Sasson SZ, Seder R et al (1990) Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 172(3):921–929
Swain SL, Weinberg AD, English M et al (1990) IL-4 directs the development of Th2-like helper effectors. J Immunol 145(11):3796–3806
Mercer F, Khaitan A, Kozhaya L et al (2014) Differentiation of IL-17-producing effector and regulatory human T cells from lineage-committed naive precursors. J Immunol 193(3):1047–1054. doi:10.4049/jimmunol.1302936
Takeshita M, Suzuki K, Kassai Y et al (2015) Polarization diversity of human CD4+ stem cell memory T cells. Clin Immunol 159(1):107–117. doi:10.1016/j.clim.2015.04.010
Manel N, Unutmaz D, Littman DR (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9(6):641–649. doi:10.1038/ni.1610
Veldhoen M, Hirota K, Christensen J et al (2008) Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J Exp Med 206(1):43–49. doi:10.1084/jem.20081438
Cosmi L, De Palma R, Santarlasci V et al (2008) Human interleukin 17-producing cells originate from a CD161 + CD4+ T cell precursor. J Exp Med 205(8):1903–1916. doi:10.1084/jem.20080397
Kastirr I, Crosti M, Maglie S et al (2015) Signal strength and metabolic requirements control cytokine-induced Th17 differentiation of uncommitted human T cells. J Immunol 195(8):3617–3627. doi:10.4049/jimmunol.1501016
Mazzoni A, Santarlasci V, Maggi L et al (2015) Demethylation of the RORC2 and IL17A in human CD4+ T lymphocytes defines Th17 origin of nonclassic Th1 cells. J Immunol 194(7):3116–3126. doi:10.4049/jimmunol.1401303
Santarlasci V, Maggi L, Capone M et al (2009) TGF-beta indirectly favors the development of human Th17 cells by inhibiting Th1 cells. Eur J Immunol 39(1):207–215. doi:10.1002/eji.200838748
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media New York
About this protocol
Cite this protocol
Annunziato, F., Maggi, L. (2017). Strategies for T Helper Cell Subset Differentiation from Naïve Precursors. In: Lugli, E. (eds) T-Cell Differentiation. Methods in Molecular Biology, vol 1514. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6548-9_11
Download citation
DOI: https://doi.org/10.1007/978-1-4939-6548-9_11
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-6546-5
Online ISBN: 978-1-4939-6548-9
eBook Packages: Springer Protocols