Skip to main content
SpringerLink
Log in

Notch and T Cell Function – A Complex Tale

  • Chapter
  • First Online:
Molecular Mechanisms of Notch Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1066))

Abstract

Notch drives critical decisions in a multitude of developmental decisions in many invertebrate and vertebrate organisms including flies, worms, fish, mice and humans. Therefore, it is not surprising that Notch family members also play a key role in cell fate choices in the vertebrate immune system. This review highlights the critical function of Notch in the development of mature T lymphocytes from hematopoietic precursors and describes the role of Notch in mature T cell activation, proliferation and differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CTL:

Cytotoxic T lymphocytes.

Dll:

Delta-like

GSI, γ:

Secretase inhibitor

IFNχ:

Interferon gamma

IL17:

Interleukin 17

IL2:

Interleukin 2

IL4:

Interleukin 4

Jag:

Jagged

NICD:

Notch intracellular domain

RBPJ:

Recombination signal binding protein for immunoglobulin kappa J region

Tregs:

T regulatory cells

References

  • Adler SH, Chiffoleau E, Xu L, Dalton NM, Burg JM, Well AD, Wolfe MS, Turka LA, Pear WS (2003) Notch signaling augments T cell responsiveness by enhancing CD25 expression. J Immunol 171(6):2896–2903

    Article  CAS  PubMed  Google Scholar 

  • Alam MS, Maekawa Y, Kitamura A, Tanigaki K, Yoshimoto T, Kishihara K, Yasutomo K (2010) Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A 107(13):5943–5948

    Article  PubMed  PubMed Central  Google Scholar 

  • Amsen D, Blander JM, Lee GR, Tanigaki K, Honjo T, Flavell RA (2004) Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 117(4):515–526

    Article  CAS  PubMed  Google Scholar 

  • Amsen D, Antov A, Jankovic D, Sher A, Radtke F, Souabni A, Busslinger M, McCright B, Gridley T, Flavell RA (2007) Direct regulation of Gata3 expression determines the T helper differentiation potential of notch. Immunity 27(1):89–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amsen D, Helbig C, Backer RA (2015) Notch in T cell differentiation: all things considered. Trends Immunol 36(12):802–814

    Article  CAS  PubMed  Google Scholar 

  • Anastasi E, Campese AF, Bellavia D, Bulotta A, Balestri A, Pascucci M, Checquolo S, Gradini R, Lendahl U, Frati L, Gulino A, Di Mario U, Screpanti I (2003) Expression of activated Notch3 in transgenic mice enhances generation of T regulatory cells and protects against experimental autoimmune diabetes. J Immunol 171(9):4504–4511

    Article  CAS  PubMed  Google Scholar 

  • Auderset F, Schuster S, Coutaz M, Koch U, Desgranges F, Merck E, MacDonald HR, Radtke F, Tacchini-Cottier F (2012) Redundant Notch1 and Notch2 signaling is necessary for IFNgamma secretion by T helper 1 cells during infection with Leishmania major. PLoS Pathog 8(3):e1002560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ayaz F, Osborne BA (2014) Non-canonical notch signaling in cancer and immunity. Front Oncol 4(345):1–6

    Google Scholar 

  • Backer RA, Helbig C, Gentek R, Kent A, Laidlaw BJ, Dominguez CX, de Souza YS, van Trierum SE, van Beek R, Rimmelzwaan GF, ten Brinke A, Willemsen AM, van Kampen AH, Kaech SM, Blander JM, van Gisbergen K, Amsen D (2014) A central role for notch in effector CD8(+) T cell differentiation. Nat Immunol 15(12):1143–1151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barbarulo A, Grazioli P, Campese AF, Bellavia D, Di Mario G, Pelullo M, Ciuffetta A, Colantoni S, Vacca A, Frati L, Gulino A, Felli MP, Screpanti I (2011) Notch3 and canonical NF-kappaB signaling pathways cooperatively regulate Foxp3 transcription. J Immunol 186(11):6199–6206

    Article  CAS  PubMed  Google Scholar 

  • Bassil R, Zhu B, Lahoud Y, Riella LV, Yagita H, Elyaman W, Khoury SJ (2011) Notch ligand delta-like 4 blockade alleviates experimental autoimmune encephalomyelitis by promoting regulatory T cell development. J Immunol 187(5):2322–2328

    Article  CAS  PubMed  Google Scholar 

  • Benson RA, Adamson K, Corsin-Jimenez M, Marley JV, Wahl KA, Lamb JR, Howie SE (2005) Notch1 co-localizes with CD4 on activated T cells and notch signaling is required for IL-10 production. Eur J Immunol 35(3):859–869

    Article  CAS  PubMed  Google Scholar 

  • Bray SJ (2016) Notch signalling in context. Nat Rev Mol Cell Biol 17(11):722–735

    Article  CAS  PubMed  Google Scholar 

  • Charbonnier LM, Wang S, Georgiev P, Sefik E, Chatila TA (2015) Control of peripheral tolerance by regulatory T cell-intrinsic notch signaling. Nat Immunol 16(11):1162–1173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiang MY, Radojcic V, Maillard I (2016) Oncogenic notch signaling in T-cell and B-cell lymphoproliferative disorders. Curr Opin Hematol 23(4):362–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho OH, Shin HM, Miele L, Golde TE, Fauq A, Minter LM, Osborne BA (2009) Notch regulates cytolytic effector function in CD8+ T cells. J Immunol 182(6):3380–3389

    Article  CAS  PubMed  Google Scholar 

  • Ciofani M, Zúñiga-Pflücker JC (2005) Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 6(9):881–888

    Article  CAS  PubMed  Google Scholar 

  • Ciofani M, Schmitt TM, Ciofani A, Michie AM, Cuburu N, Aublin A, Maryanski JL, Zúñiga-Pflücker JC (2004) Obligatory role for cooperative signaling by pre-TCR and notch during thymocyte differentiation. J Immunol 172(9):5230–5239

    Article  CAS  PubMed  Google Scholar 

  • Dinesh RK, Skaggs BJ, La Cava A, Hahn BH, Singh RP (2010) CD8+ Tregs in lupus, autoimmunity, and beyond. Autoimmun Rev 9(8):560–568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dongre A, Surampudi L, Lawlor RG, Fauq AH, Miele L, Golde TE, Minter LM, Osborne BA (2014) Non-canonical notch signaling drives activation and differentiation of peripheral CD4(+) T cells. Front Immunol 5:54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, Sklar J (1991) TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66(4):649–661

    Article  CAS  PubMed  Google Scholar 

  • Elyaman W, Bassil R, Bradshaw EM, Orent W, Lahoud Y, Zhu B, Radtke F, Yagita H, Khoury SJ (2012) Notch receptors and Smad3 signaling cooperate in the induction of interleukin-9-producing T cells. Immunity 36(4):623–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang TC, Yashiro-Ohtani Y, Del Bianco C, Knoblock DM, Blacklow SC, Pear WS (2007) Notch directly regulates Gata3 expression during T helper 2 cell differentiation. Immunity 27(1):100–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Golde TE, Koo EH, Felsenstein KM, Osborne BA, Miele L (2013) γ-Secretase inhibitors and modulators. Biochim Biophys Acta 1828(12):2898–2907

    Article  CAS  PubMed  Google Scholar 

  • Hori K, Sen A, Kirchhausen T, Artavanis-Tsakonas S (2011) Synergy between theESCRT-III complex and Deltex defines a ligand-independent notch signal. J Cell Biol 195(6):1005–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoyne GF, Le Roux I, Corsin-Jimenez M, Tan K, Dunne J, Forsyth LM, Dallman MJ, Owen MJ, Ish-Horowicz D, Lamb JR (2000) Serrate1-induced notch signalling regulates the decision between immunity and tolerance made by peripheral CD4(+) T cells. Int Immunol 12(2):177–185

    Article  CAS  PubMed  Google Scholar 

  • Izon DJ, Aster JC, He Y, Weng A, Karnell FG, Patriub V, Xu L, Bakkour S, Rodriguez C, Allman D, Pear WS (2002) Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1. Immunity 16(2):231–243

    Article  CAS  PubMed  Google Scholar 

  • Jaleco AC, Neves H, Hooijberg E, Gameiro P, Clode N, Haury M, Henrique D, Parreira L (2001) Differential effects of notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. J Exp Med 194(7):991–1002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keerthivasan S, Suleiman R, Lawlor R, Roderick J, Bates T, Minter L, Anguita J, Juncadella I, Nickoloff BJ, Le Poole IC, Miele L, Osborne BA (2011) Notch signaling regulates mouse and human Th17 differentiation. J Immunol 187(2):692–701

    Article  CAS  PubMed  Google Scholar 

  • Koch U, Lacombe TA, Holland D, Bowman JL, Cohen BL, Egan SE, Guidos CJ (2001) Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated inhibition of Notch-1. Immunity 15(2):225–236

    Article  CAS  PubMed  Google Scholar 

  • Kuijk LM, Verstege MI, Rekers NV, Bruijns SC, Hooijberg E, Roep BO, de Gruijl TD, van Kooyk Y, Unger WW (2013) Notch controls generation and function of human effector CD8+ T cells. Blood 121(14):2638–2646

    Article  CAS  PubMed  Google Scholar 

  • Kuksin CA, Minter LM (2015) The link between autoimmunity and lymphoma: does NOTCH signaling play a contributing role? Front Oncol 5:51. https://doi.org/10.3389/fonc.2015.00051

    Article  PubMed  PubMed Central  Google Scholar 

  • Laky K, Evans S, Perez-Diez A, Fowlkes BJ (2015) Notch signaling regulates antigen sensitivity of naive CD4+ T cells by tuning co-stimulation. Immunity 42(1):80–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehar SM, Dooley J, Farr AG, Bevan MJ (2005) Notch ligands Delta 1 and Jagged1 transmit distinct signals to T-cell precursors. Blood 105(4):1440–1447

    Article  CAS  PubMed  Google Scholar 

  • Maekawa Y, Tsukumo S, Chiba S, Hirai H, Hayashi Y, Okada H, Kishihara K, Yasutomo K (2003) Delta1-Notch3 interactions bias the functional differentiation of activated CD4+ T cells. Immunity 19(4):549–559

    Article  CAS  PubMed  Google Scholar 

  • Maekawa Y, Minato Y, Ishifune C, Kurihara T, Kitamura A, Kojima H, Yagita H, Sakata-Yanagimoto M, Saito T, Taniuchi I, Chiba S, Sone S, Yasutomo K (2008) Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nat Immunol 9(10):1140–1147

    Article  CAS  PubMed  Google Scholar 

  • Mathieu M, Cotta-Grand N, Daudelin JF, Thebault P, Labrecque N (2013) Notch signaling regulates PD-1 expression during CD8(+) T-cell activation. Immunol Cell Biol 91(1):82–88

    Article  CAS  PubMed  Google Scholar 

  • Mathieu M, Duval F, Daudelin JF, Labrecque N (2015) The notch signaling pathway controls short-lived effector CD8+ T cell differentiation but is dispensable for memory generation. J Immunol 194(12):5654–5662

    Article  CAS  PubMed  Google Scholar 

  • Minter LM, Turley DM, Das P, Shin HM, Joshi I, Lawlor RG, Cho OH, Palaga T, Gattipati S, Telfer JC, Kostura L, Fauq AH, Simpson K, Such KA, Miele L, Golde TE, Miller SD, Osborne BA (2005) Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing notch upregulation of Tbx21. Nat Immunol 6(7):680–688

    Article  CAS  PubMed  Google Scholar 

  • Mota C, Nunes-Silva V, Pires AR, Matoso P, Victorino RM, Sousa AE, Caramalho I (2014) Delta-like 1-mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells. J Immunol 193(12):5854–5862

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee S, Schaller MA, Neupane R, Kunkel SL, Lukacs NW (2009) Regulation of T cell activation by notch ligand, DLL4, promotes IL-17 production and Rorc activation. J Immunol 182(12):7381–7388

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee T, Kim WS, Mandal L, Banerjee U (2011) Interaction between notch and Hif-alpha in development and survival of Drosophila blood cells. Science 332(6034):1210–1213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oswald F, Rodriguez P, Giaimo BD, Antonello ZA, Mira L, Mittler G, Thiel VN, Collins KJ, Tabaja N, Cizelsky W, Rothe M, Kühl SJ, Kühl M, Ferrante F, Hein K, Kovall RA, Dominguez M, Borggrefe T (2016) A phospho-dependent mechanism involving NCoR and KMT2D controls a permissive chromatin state at Notch target genes. Nucleic Acids Res 44(10):4703–4720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ou-Yang HF, Zhang HW, Wu CG, Zhang P, Zhang J, Li JC, Hou LH, He F, Ti XY, Song LQ, Zhang SZ, Feng L, Qi HW, Han H (2009) Notch signaling regulates the FOXP3 promoter through RBP-J- and Hes1-dependent mechanisms. Mol Cell Biochem 320(1–2):109–114

    Article  CAS  PubMed  Google Scholar 

  • Palaga T, Miele L, Golde TE, Osborne BA (2003) TCR-mediated notch signaling regulates proliferation and IFN-gamma production in peripheral T cells. J Immunol 171(6):3019–3024

    Article  CAS  PubMed  Google Scholar 

  • Perumalsamy LR, Nagala M, Banerjee P, Sarin A (2009) A hierarchical cascade activated by non-canonical notch signaling and the mTOR-Rictor complex regulates neglect-induced death in mammalian cells. Cell Death Differ 16(6):879–889

    Article  CAS  PubMed  Google Scholar 

  • Perumalsamy LR, Nagala M, Sarin A (2010) Notch-activated signaling cascade interacts with mitochondrial remodeling proteins to regulate cell survival. Proc Natl Acad Sci U S A 107(15):6882–6887

    Article  PubMed  PubMed Central  Google Scholar 

  • Rand MD, Grimm LM, Artavanis-Tsakonas S, Patriub V, Blacklow SC, Sklar J, Aster JC (2000) Calcium depletion dissociates and activates heterodimeric notch receptors. Mol Cell Biol 20(5):1825–1835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robey E, Chang D, Itano A, Cado D, Alexander H, Lans D, Weinmaster G, Salmon P (1996) An activated form of notch influences the choice between CD4 and CD8 T cell lineages. Cell 87(3):483–492

    Article  CAS  PubMed  Google Scholar 

  • Roderick JE, Gonzalez-Perez G, Kuksin CA, Dongre A, Roberts ER, Srinivasan J, Andrzejewski C Jr, Fauq AH, Golde TE, Miele L, Minter LM (2013) Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia. J Exp Med 210(7):1311–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rothenberg EV, Ungerbäck J, Champhekar A (2016) Forging T-lymphocyte identity: intersecting networks of transcriptional control. Adv Immunol 129:109–174

    Article  PubMed  Google Scholar 

  • Rutz S, Mordmuller B, Sakano S, Scheffold A (2005) Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cells. Eur J Immunol 35(8):2443–2451

    Article  CAS  PubMed  Google Scholar 

  • Rutz S, Janke M, Kassner N, Hohnstein T, Krueger M, Scheffold A (2008) Notch regulates IL-10 production by T helper 1 cells. Proc Natl Acad Sci U S A 105(9):3497–3502

    Article  PubMed  PubMed Central  Google Scholar 

  • Sade H, Krishna S, Sarin A (2004) The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells. J Biol Chem 279(4):2937–2944

    Article  CAS  PubMed  Google Scholar 

  • Samon JB, Champhekar A, Minter LM, Telfer JC, Miele L, Fauq A, Das P, Golde TE, Osborne BA (2008) Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells. Blood 112(5):1813–1821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitt TM, Zúñiga-Pflücker JC (2002) Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 17(6):749–756

    Article  CAS  PubMed  Google Scholar 

  • Schmitt TM, Ciofani M, Petrie HT, Zúñiga-Pflücker JC (2004) Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions. J Exp Med 200(4):469–479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah DK, Zúñiga-Pflücker JC (2014) An overview of the intrathymic intricacies of T cell development. J Immunol 192(9):4017–4023

    Article  CAS  PubMed  Google Scholar 

  • Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, Golde TE, Sonenshein GE, Osborne BA (2006) Notch1 augments NF-kappaB activity by facilitating its nuclear retention. EMBO J 25(1):129–138

    Article  CAS  PubMed  Google Scholar 

  • Shin HM, Tilahun ME, Cho OH, Chandiran K, Kuksin CA, Keerthivasan S, Fauq AH, Golde TE, Miele L, Thome M, Osborne BA, Minter LM (2014) NOTCH1 can initiate NF-κB activation via cytosolic interactions with components of the T cell signalosome. Front Immunol 5:249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sierra RA, Thevenot P, Raber PL, Cui Y, Parsons C, Ochoa AC, Trillo-Tinoco J, Del Valle L, Rodriguez PC (2014) Rescue of notch-1 signaling in antigen-specific CD8+ T cells overcomes tumor-induced T-cell suppression and enhances immunotherapy in cancer. Cancer Immunol Res 2(8):800–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skokos D, Nussenzweig MC (2007) CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 notch-like ligand in response to bacterial LPS. J Exp Med 204(7):1525–1531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, Chiba S, Shimada M, Yasutomo K (2010) Notch2 signaling is required for potent antitumor immunity in vivo. J Immunol 184(9):4673–4678

    Article  CAS  PubMed  Google Scholar 

  • Tacchini-Cottier F, Allenbach C, Otten LA, Radtke F (2004) Notch1 expression on T cells is not required for CD4+ T helper differentiation. Eur J Immunol 34(6):1588–1596

    Article  CAS  PubMed  Google Scholar 

  • Tanaka S, Tsukada J, Suzuki W, Hayashi K, Tanigaki K, Tsuji M, Inoue H, Honjo T, Kubo M (2006) The interleukin-4 enhancer CNS-2 is regulated by notch signals and controls initial expression in NKT cells and memory-type CD4 T cells. Immunity 24(6):689–701

    Article  CAS  PubMed  Google Scholar 

  • Tang XL, Smith TR, Kumar V (2005) Specific control of immunity by regulatory CD8 T cells. Cell Mol Immunol 2(1):11–19

    PubMed  CAS  Google Scholar 

  • Tran IT, Sandy AR, Carulli AJ, Ebens C, Chung J, Shan GT, Radojcic V, Friedman A, Gridley T, Shelton A, Reddy P, Samuelson LC, Yan M, Siebel CW, Maillard I (2013) Blockade of individual notch ligands and receptors controls graft-versus-host disease. J Clin Investig 123(4):1590–1604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Tetering G, van Diest P, Verlaan I, van der Wall E, Kopan R, Vooijs M (2009) Metalloprotease ADAM10 is required for Notch1 site 2 cleavage. J Biol Chem 284(45):31018–31027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vigouroux S, Yvon E, Wagner HJ, Biagi E, Dotti G, Sili U, Lira C, Rooney CM, Brenner MK (2003) Induction of antigen-specific regulatory T cells following overexpression of a notch ligand by human B lymphocytes. J Virol 77(20):10872–10880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson A, MacDonald HR, Radtke F (2001) Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus. J Exp Med 194(7):1003–1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolfer A, Bakker T, Wilson A, Nicolas M, Ioannidis V, Littman DR, Wilson CB, Held W, Robson MacDonald H, Radtke F (2001) Inactivation of Notch1 in immature thymocytes does not perturb CD4 or CD8 T cell development. Nat Immunol 2(3):235–241

    Article  CAS  PubMed  Google Scholar 

  • Wong KK, Carpenter MJ, Young LL, Walker SJ, McKenzie G, Rust AJ, Ward G, Packwood L, Wahl K, Dalriviere L, Hoyne G, Gibbs P, Champion BR, Lamb JR, Dallman MJ (2003) Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8+ cell-dependent mechanism. J Clin Invest 112(11):1741–1750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yvon ES, Vigouroux S, Rousseau RF, Biagi E, Amrolia P, Dotti G, Wagner HJ, Brenner MK (2003) Overexpression of the notch ligand, Jagged-1, induces alloantigen-specific human regulatory T cells. Blood 102(10):3815–3821

    Article  CAS  PubMed  Google Scholar 

  • Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations. Annu Rev Immunol 28:445–489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank the members of the Osborne and Minter labs for lively discussions and the National Multiple Sclerosis Society (RG 5151A1/2) and the NIH (CA166009) for support.

Author information

Authors and Affiliations

  1. Department of Veterinary & Animal Sciences, Program in Animal Biotechnology and Biomedical Sciences, University of Massachusetts, Amherst, MA, USA

    Jyothi Vijayaraghavan & Barbara A. Osborne

  2. Program in Molecular & Cellular Biology, University of Massachusetts, Amherst, MA, USA

    Barbara A. Osborne

Authors
  1. Jyothi Vijayaraghavan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara A. Osborne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara A. Osborne .

Editor information

Editors and Affiliations

  1. Institute of Biochemistry, University of Giessen, Giessen, Germany

    Tilman Borggrefe

  2. Institute of Biochemistry, University of Giessen, Giessen, Germany

    Benedetto Daniele Giaimo

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vijayaraghavan, J., Osborne, B.A. (2018). Notch and T Cell Function – A Complex Tale. In: Borggrefe, T., Giaimo, B. (eds) Molecular Mechanisms of Notch Signaling. Advances in Experimental Medicine and Biology, vol 1066. Springer, Cham. https://doi.org/10.1007/978-3-319-89512-3_17

Download citation

Publish with us

Policies and ethics

Search

Navigation