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Tcf1 at the crossroads of CD4+ and CD8+ T cell identity

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Frontiers in Biology

Abstract

Transcription factors and DNA/histone modification enzymes work in concert to establish and maintain cell identity. CD4+ and CD8+ T cells are key players in cellular immunity with distinct functions. Recent studies offer novel insights into how their identities are established in the thymus and maintained in the periphery during immune responses. During thymic maturation, Thpok, HDAC1 and HDAC2 guard CD4+ T cells from activation of CD8+ cytotoxic genes, and Tcf1 and Lef1 utilize their intrinsic HDAC activity to shut down CD4+ lineage-associated genes in CD8+ T cells. In activated CD4+ T cells, Tcf1 and Lef1 act upstream of the Bcl6-Blimp1 axis to direct differentiation of follicular helper T (Tfh) cells, and prevent diversion of Tfh to IL-17-producing cells. In parallel, T-bet, together with Eomes or Blimp1, ensures proper induction of the cytotoxic program in CD8+ effectors elicited by acute infection, and prevents generation of pathogenic, IL-17-producing CD8+ effector T cells. Antigen persistence due to chronic viral infection leads to CD8+ T cell exhaustion. A portion of exhausted CD8+ T cells has the capacity to activate the Tfh program in a Tcf1-dependent manner. Those Tfh-like CD8+ Tcells exhibit enhanced proliferative capacity in response to PD-1 blockage therapy and are more effective in curtailing viral replication. Thus, dissecting the molecular aspects of T cell identity, during development and immune responses, may lead to new therapies for treating autoimmunity, tumors, and persistent infections.

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References

  • Banga R, Procopio F A, Noto A, Pollakis G, Cavassini M, Ohmiti K, Corpataux J M, de Leval L, Pantaleo G, Perreau M (2016). PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat Med, 22(7): 754–761

    Article  CAS  PubMed  Google Scholar 

  • Boucheron N, Tschismarov R, Goschl L, Moser M A, Lagger S, Sakaguchi S, Winter M, Lenz F, Vitko D, Breitwieser F P, Müller L, Hassan H, Bennett K L, Colinge J, Schreiner W, Egawa T, Taniuchi I, Matthias P, Seiser C, Ellmeier W (2014). CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2. Nat Immunol, 15(5): 439–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cannarile MA, Lind N A, Rivera R, Sheridan A D, Camfield K A, Wu B B, Cheung K P, Ding Z, Goldrath A W (2006). Transcriptional regulator Id2 mediates CD8+ T cell immunity. Nat Immunol, 7(12): 1317–1325

    Article  CAS  PubMed  Google Scholar 

  • Choi Y S, Gullicksrud J A, Xing S, Zeng Z, Shan Q, Li F, Love P E, Peng W, Xue H H, Crotty S (2015). LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6. Nat Immunol, 16(9): 980–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cobaleda C, Jochum W, Busslinger M (2007). Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature, 449(7161): 473–477

    Article  CAS  PubMed  Google Scholar 

  • Collins A, Littman D R, Taniuchi I (2009). RUNX proteins in transcription factor networks that regulate T-cell lineage choice. Nat Rev Immunol, 9(2): 106–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crotty S (2014). T follicular helper cell differentiation, function, and roles in disease. Immunity, 41(4): 529–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Obaldia M E, Bhandoola A (2015). Transcriptional regulation of innate and adaptive lymphocyte lineages. Annu Rev Immunol, 33(1): 607–642

    Article  PubMed  Google Scholar 

  • Fukazawa Y, Lum R, Okoye A A, Park H, Matsuda K, Bae J Y, Hagen S I, Shoemaker R, Deleage C, Lucero C, Morcock D, Swanson T, Legasse A W, Axthelm MK, Hesselgesser J, Geleziunas R, Hirsch V M, Edlefsen P T, Piatak M, Estes J D, Lifson J D, Picker L J (2015). B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med, 21(2): 132–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Germar K, Dose M, Konstantinou T, Zhang J, Wang H, Lobry C, Arnett K L, Blacklow S C, Aifantis I, Aster J C, Gounari F (2011). T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling. Proc Natl Acad Sci USA, 108(50): 20060–20065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giese K, Cox J, Grosschedl R (1992). The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell, 69(1): 185–195

    Article  CAS  PubMed  Google Scholar 

  • Harty J T, Badovinac V P (2008). Shaping and reshaping CD8+ T-cell memory. Nat Rev Immunol, 8(2): 107–119

    Article  CAS  PubMed  Google Scholar 

  • Hatzi K, Nance J P, Kroenke MA, Bothwell M, Haddad E K, Melnick A, Crotty S (2015). BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms. J Exp Med, 212(4): 539–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He R, Hou S, Liu C, Zhang A, Bai Q, Han M, Yang Y, Wei G, Shen T, Yang X, Xu L, Chen X, Hao Y, Wang P, Zhu C, Ou J, Liang H, Ni T, Zhang X, Zhou X, Deng K, Chen Y, Luo Y, Xu J, Qi H, Wu Y, Ye L (2016). Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection. Nature, 537(7620): 412–428

    Article  CAS  PubMed  Google Scholar 

  • Im S J, Hashimoto M, Gerner M Y, Lee J, Kissick H T, Burger M C, Shan Q, Hale J S, Lee J, Nasti T H, Sharpe A H, Freeman G J, Germain R N, Nakaya H I, Xue H H, Ahmed R (2016). Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature, 537(7620): 417–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Intlekofer A M, Banerjee A, Takemoto N, Gordon S M, Dejong C S, Shin H, Hunter C A, Wherry E J, Lindsten T, Reiner S L (2008). Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science, 321(5887): 408–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ioannidis V, Beermann F, Clevers H, Held W (2001). The beta-catenin–TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival. Nat Immunol, 2(8): 691–697

    Article  CAS  PubMed  Google Scholar 

  • Ji Y, Pos Z, Rao M, Klebanoff C A, Yu Z, Sukumar M, Reger R N, Palmer D C, Borman Z A, Muranski P, Wang E, Schrump D S, Marincola F M, Restifo N P, Gattinoni L (2011). Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nat Immunol, 12(12): 1230–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joshi N S, Cui W, Chandele A, Lee H K, Urso D R, Hagman J, Gapin L, Kaech S M (2007). Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity, 27(2): 281–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kallies A, Xin A, Belz G T, Nutt S L (2009). Blimp-1 transcription factor is required for the differentiation of effector CD8(+) T cells and memory responses. Immunity, 31(2): 283–295

    Article  CAS  PubMed  Google Scholar 

  • Kee B L (2009). E and ID proteins branch out. Nat Rev Immunol, 9(3): 175–184

    Article  CAS  PubMed  Google Scholar 

  • Khaitan A, Unutmaz D (2011). Revisiting immune exhaustion during HIV infection. Curr HIV/AIDS Rep, 8(1): 4–11

    Article  PubMed  PubMed Central  Google Scholar 

  • Leong Y A, Chen Y, Ong H S, Wu D, Man K, Deleage C, Minnich M, Meckiff B J, Wei Y, Hou Z, Zotos D, Fenix K A, Atnerkar A, Preston S, Chipman J G, Beilman G J, Allison C C, Sun L, Wang P, Xu J, Toe J G, Lu H K, Tao Y, Palendira U, Dent A L, Landay A L, Pellegrini M, Comerford I, Mc Coll S R, Schacker T W, Long H M, Estes J D, Busslinger M, Belz G T, Lewin S R, Kallies A, Yu D (2016). CXCR5 (+) follicular cytotoxic T cells control viral infection in B cell follicles. Nat Immunol, 17(10): 1187–1196

    Article  CAS  PubMed  Google Scholar 

  • Li P, Burke S, Wang J, Chen X, Ortiz M, Lee S C, Lu D, Campos L, Goulding D, Ng B L, Dougan G, Huntly B, Gottgens B, Jenkins N A, Copeland N G, Colucci F, Liu P (2010). Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science, 329(5987): 85–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X, Chen X, Zhong B, Wang A, Wang X, Chu F, Nurieva R I, Yan X, Chen P, van der Flier L G, Nakatsukasa H, Neelapu S S, Chen W, Clevers H, Tian Q, Qi H, Wei L, Dong C (2014). Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development. Nature, 507(7493): 513–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma J, Wang R, Fang X, Ding Y, Sun Z (2011). Critical role of TCF-1 in repression of the IL-17 gene. PLoS One, 6(9): e24768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malhotra N, Narayan K, Cho O H, Sylvia K E, Yin C, Melichar H, Rashighi M, Lefebvre V, Harris J E, Berg L J, Kang J (2013). A network of high-mobility group box transcription factors programs innate interleukin-17 production. Immunity, 38(4): 681–693

    Article  CAS  PubMed  Google Scholar 

  • Mielke L A, Groom J R, Rankin L C, Seillet C, Masson F, Putoczki T, Belz G T (2013). TCF-1 controls ILC2 and NKp46 + RORt + innate lymphocyte differentiation and protection in intestinal inflammation. J Immunol, 191(8): 4383–4391

    Article  CAS  PubMed  Google Scholar 

  • Mingueneau M, Kreslavsky T, Gray D, Heng T, Cruse R, Ericson J, Bendall S, Spitzer M H, Nolan G P, Kobayashi K, von Boehmer H, Mathis D, Benoist C, Best A J, Knell J, Goldrath A, Jojic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao T N, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman N A, Sun J C, Min-Oo G, Kim C C, Lanier L L, Miller J, Brown B, Merad M, Gautier E L, Jakubzick C, Randolph G J, Monach P, Blair D A, Dustin M L, Shinton S A, Hardy R R, Laidlaw D, Collins J, Gazit R, Rossi D J, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S (2013). The transcriptional landscape of alphabeta T cell differentiation. Nat Immunol, 14(6): 619–632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mittrucker H W, Visekruna A, Huber M (2014). Heterogeneity in the differentiation and function of CD8(+) T cells. Arch Immunol Ther Exp (Warsz), 62(6): 449–458

    Article  Google Scholar 

  • Mucida D, Husain M M, Muroi S, van Wijk F, Shinnakasu R, Naoe Y, Reis B S, Huang Y, Lambolez F, Docherty M, Attinger A, Shui J W, Kim G, Lena C J, Sakaguchi S, Miyamoto C, Wang P, Atarashi K, Park Y, Nakayama T, Honda K, Ellmeier W, Kronenberg M, Taniuchi I, Cheroutre H (2013). Transcriptional reprogramming of mature CD4(+) helper T cells generates distinct MHC class IIrestricted cytotoxic T lymphocytes. Nat Immunol, 14(3): 281–289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muroi S, Naoe Y, Miyamoto C, Akiyama K, Ikawa T, Masuda K, Kawamoto H, Taniuchi I (2008). Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate. Nat Immunol, 9(10): 1113–1121

    Article  CAS  PubMed  Google Scholar 

  • Natoli G (2010). Maintaining cell identity through global control of genomic organization. Immunity, 33(1): 12–24

    Article  CAS  PubMed  Google Scholar 

  • Paley MA, Kroy D C, Odorizzi P M, Johnnidis J B, Dolfi D V, Barnett B E, Bikoff E K, Robertson E J, Lauer G M, Reiner S L, Wherry E J (2012). Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection. Science, 338(6111): 1220–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pearce E L, Mullen A C, Martins G A, Krawczyk C M, Hutchins A S, Zediak V P, Banica M, Di Cioccio C B, Gross D A, Mao C A, Shen H, Cereb N, Yang S Y, Lindsten T, Rossant J, Hunter C A, Reiner S L (2003). Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science, 302(5647): 1041–1043

    Article  CAS  PubMed  Google Scholar 

  • Quigley M F, Gonzalez V D, Granath A, Andersson J, Sandberg J K (2007). CXCR5 + CCR7-CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles. Eur J Immunol, 37(12): 3352–3362

    Article  CAS  PubMed  Google Scholar 

  • Reis B S, Rogoz A, Costa-Pinto F A, Taniuchi I, Mucida D (2013). Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4(+) T cell immunity. Nat Immunol, 14(3): 271–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rui J, Liu H, Zhu X, Cui Y, Liu X (2012). Epigenetic silencing of CD8 genes by ThPOK-mediated deacetylation during CD4 T cell differentiation. J Immunol, 189(3): 1380–1390

    Article  CAS  PubMed  Google Scholar 

  • Rutishauser R L, Martins G A, Kalachikov S, Chandele A, Parish I A, Meffre E, Jacob J, Calame K, Kaech S M (2009). Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties. Immunity, 31(2): 296–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaw L A, Belanger S, Omilusik K D, Cho S, Scott-Browne J P, Nance J P, Goulding J, Lasorella A, Lu L F, Crotty S, Goldrath A W (2016). Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation. Nat Immunol, 17(7): 834–843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin H, Blackburn S D, Intlekofer A M, Kao C, Angelosanto J M, Reiner S L, Wherry E J (2009). A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection. Immunity, 31(2): 309–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shy B R, Wu C I, Khramtsova G F, Zhang J Y, Olopade O I, Goss K H, Merrill B J (2013). Regulation of Tcf7l1 DNA binding and protein stability as principal mechanisms of Wnt/beta-catenin signaling. Cell Reports, 4(1): 1–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smale S T (2003). The establishment and maintenance of lymphocyte identity through gene silencing. Nat Immunol, 4(7): 607–615

    Article  CAS  PubMed  Google Scholar 

  • Staal F J, Sen JM (2008). The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur J Immunol, 38: 1788–1794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinke F C, Xue H H (2014). From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells. Immunol Res, 59(1–3): 45–55

    Article  CAS  PubMed  Google Scholar 

  • Steinke F C, Yu S, Zhou X, He B, Yang W, Zhou B, Kawamoto H, Zhu J, Tan K, Xue H H (2014). TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells. Nat Immunol, 15(7): 646–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taniuchi I, Ellmeier W (2011). Transcriptional and epigenetic regulation of CD4/CD8 lineage choice. Adv Immunol, 110: 71–110

    Article  CAS  PubMed  Google Scholar 

  • Utzschneider D T, Charmoy M, Chennupati V, Pousse L, Ferreira D P, Calderon-Copete S, Danilo M, Alfei F, Hofmann M, Wieland D, Pradervand S, Thimme R, Zehn D, Held W (2016). T Cell Factor 1-Expressing memory-like CD8(+) T cells sustain the immune response to chronic viral infections. Immunity, 45(2): 415–427

    Article  CAS  PubMed  Google Scholar 

  • Vacchio M S, Bosselut R (2016). What happens in the thymus does not stay in the thymus: How T cells recycle the CD4+-CD8+ lineage commitment transcriptional circuitry to control their function. J Immunol, 196(12): 4848–4856

    Article  CAS  PubMed  Google Scholar 

  • Vacchio MS, Wang L, Bouladoux N, Carpenter A C, Xiong Y, Williams L C, Wohlfert E, Song K D, Belkaid Y, Love P E, Bosselut R (2014). A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells. Nat Immunol, 15(10): 947–956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weber B N, Chi A W, Chavez A, Yashiro-Ohtani Y, Yang Q, Shestova O, Bhandoola A (2011). A critical role for TCF-1 in T-lineage specification and differentiation. Nature, 476(7358): 63–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wherry E J, Kurachi M (2015). Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol, 15(8): 486–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams M A, Bevan M J (2007). Effector and memory CTL differentiation. Annu Rev Immunol, 25(1): 171–192

    Article  CAS  PubMed  Google Scholar 

  • Wu, T., Shin, H.M., Moseman, E.A., Ji, Y., Huang, B., Harly, C., Sen, J. M., Berg, L.J., Gattinoni, L., McGavern, D.B., Schwartzberg P L (2015). TCF1 is required for the T follicular helper cell response to viral infection. Cell Rep, 12(12): 2099–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xin A, Masson F, Liao Y, Preston S, Guan T, Gloury R, Olshansky M, Lin J X, Li P, Speed T P, Smyth G K, Ernst M, Leonard W J, Pellegrini M, Kaech S M, Nutt S L, Shi W, Belz G T, Kallies A (2016). A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and Tbet. Nat Immunol, 17(4): 422–432

    Article  CAS  PubMed  Google Scholar 

  • Xing S, Li F, Zeng Z, Zhao Y, Yu S, Shan Q, Li Y, Phillips F C, Maina P K, Qi H H, Liu C, Zhu J, Pope R M, Musselman C A, Zeng C, Peng W, Xue H H (2016). Tcf1 and Lef1 transcription factors establish CD8(+) T cell identity through intrinsic HDAC activity. Nat Immunol, 17(6): 695–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu L, Cao Y, Xie Z, Huang Q, Bai Q, Yang X, He R, Hao Y, Wang H, Zhao T, Fan Z, Qin A, Ye J, Zhou X, Ye L, Wu Y (2015). The transcription factor TCF-1 initiates the differentiation of TFH cells during acute viral infection. Nat Immunol, 16(9): 991–999

    Article  CAS  PubMed  Google Scholar 

  • Xue H H, Zhao D M (2012). Regulation of mature T cell responses by the Wnt signaling pathway. Ann N Y Acad Sci, 1247(1): 16–33

    Article  CAS  PubMed  Google Scholar 

  • Yang C Y, Best J A, Knell J, Yang E, Sheridan A D, Jesionek A K, Li H S, Rivera R R, Lind K C, D’Cruz L M, Watowich S S, Murre C, Goldrath A W (2011). The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nat Immunol, 12(12): 1221–1229

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Lin X, Pan Y, Wang J, Chen P, Huang H, Xue H H, Gao J, Zhong X P (2016). Critical roles of mTOR complex 1 and 2 for T follicular helper cell differentiation and germinal center responses. eLife, 5. pii: e17936

    PubMed  PubMed Central  Google Scholar 

  • Yang X J, Seto E (2008). The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol, 9 (3): 206–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye B, Liu X, Li X, Kong H, Tian L, Chen Y (2015). T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance. Cell Death Dis, 6(3): e1694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi F, Pereira L, Hoffman J A, Shy B R, Yuen C M, Liu D R, Merrill B J (2011). Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal. Nat Cell Biol, 13(7): 762–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu S, Zhou X, Steinke F C, Liu C, Chen S C, Zagorodna O, Jing X, Yokota Y, Meyerholz D K, Mullighan C G, Knudson C M, Zhao D M, Xue H H (2012). The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity, 37(5): 813–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yui M A, Rothenberg E V (2014). Developmental gene networks: a triathlon on the course to T cell identity. Nat Rev Immunol, 14(8): 529–545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng H, Cohen S, Guy C, Shrestha S, Neale G, Brown S A, Cloer C, Kishton R J, Gao X, Youngblood B, Do M, Li M O, Locasale J W, Rathmell J C, Chi H (2016). mTORC1 and mTORC2 kinase signaling and glucose metabolism drive follicular helper T cell differentiation. Immunity, 45(3): 540–554

    Article  CAS  PubMed  Google Scholar 

  • Zhao D M, Yu S, Zhou X, Haring J S, Held W, Badovinac V P, Harty J T, Xue H H (2010). Constitutive activation of Wnt signaling favors generation of memory CD8 T cells. J Immunol, 184(3): 1191–1199

    Article  CAS  PubMed  Google Scholar 

  • Zhou X, Xue H H (2012). Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1. J Immunol, 189(6): 2722–2726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou X, Yu S, Zhao D M, Harty J T, Badovinac V P, Xue H H (2010). Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity, 33(2): 229–240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu J, Yamane H, Paul W E (2010). Differentiation of effector CD4 T cell populations. Annu Rev Immunol, 28(1): 445–489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Farrah C. Phillips for contributing to data in Fig. 2. J.A.G. is a recipient of the University of Iowa Presidential Graduate Research Fellowship and the Ballard and Seashore Dissertation Fellowship. H.-H. X. is supported by grants from the NIH (AI112579, AI115149, AI119160, and AI121080) and the US Department of Veteran Affairs (I01 BX002903).

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  1. Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    Jodi A. Gullicksrud, Qiang Shan & Hai-Hui Xue

  2. Interdisciplinary Immunology Graduate Program, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    Jodi A. Gullicksrud & Hai-Hui Xue

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Gullicksrud, J.A., Shan, Q. & Xue, HH. Tcf1 at the crossroads of CD4+ and CD8+ T cell identity. Front. Biol. 12, 83–93 (2017). https://doi.org/10.1007/s11515-017-1445-3

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