Abstract
T cell activation requires the integration of signals that arise from various types of receptors. Although TCR triggering is a necessary condition, it is often not sufficient to induce full T-cell activation, as reflected in cell proliferation and cytokine secretion. This has been firmly demonstrated for conventional αβ T cells, for which a large panel of costimulatory receptors has been identified. By contrast, the area remains more obscure for unconventional, innate-like γδ T cells, as the literature has been scarce and at times contradictory. Here we review the current state of the art on the costimulatory requirements of γδ T cell activation. We highlight the roles of members of the immunoglobulin (like CD28 or JAML) or tumour necrosis factor receptor (like CD27) superfamilies of coreceptors, but also of more atypical costimulatory molecules, such as NKG2D or CD46. Finally, we identify various areas where our knowledge is still markedly insufficient, hoping to provoke future research on γδ T cell costimulation.
Similar content being viewed by others
References
Smith-Garvin JE, Koretzky GA, Jordan MS (2009) T cell activation. Annu Rev Immunol 27:591–619
Acuto O, Michel F (2003) CD28-mediated co-stimulation: a quantitative support for TCR signalling. Nat Rev Immunol 3:939–951
Duttagupta PA, Boesteanu AC, Katsikis PD (2009) Costimulation signals for memory CD8+ T cells during viral infections. Crit Rev Immunol 29:469–486
Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4:336–347
Croft M (2009) The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 9:271–285
Bonneville M, O’Brien RL, Born WK (2010) Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol 10:467–478
Morita CT, Jin C, Sarikonda G, Wang H (2007) Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev 215:59–76
Nedellec S, Bonneville M, Scotet E (2010) Human Vgamma9Vdelta2 T cells: from signals to functions. Semin Immunol 22:199–206
Wang P, Malkovsky M (2000) Different roles of the CD2 and LFA-1 T-cell co-receptors for regulating cytotoxic, proliferative, and cytokine responses of human V gamma 9/V delta 2 T cells. Mol Med 6:196–207
Fraser JD, Irving BA, Crabtree GR, Weiss A (1991) Regulation of interleukin-2 gene enhancer activity by the T cell accessory molecule CD28. Science 251:313–316
Lindstein T, June CH, Ledbetter JA, Stella G, Thompson CB (1989) Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science 244:339–343
Boise LH, Minn AJ, Noel PJ, June CH, Accavitti MA, Lindsten T, Thompson CB (1995) CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL. Immunity 3:87–98
Sperling AI, Linsley PS, Barrett TA, Bluestone JA (1993) CD28-mediated costimulation is necessary for the activation of T cell receptor-gamma delta+ T lymphocytes. J Immunol 151:6043–6050
Ohteki T, MacDonald HR (1993) Expression of the CD28 costimulatory molecule on subsets of murine intestinal intraepithelial lymphocytes correlates with lineage and responsiveness. Eur J Immunol 23:1251–1255
Rakasz E, Hagen M, Sandor M, Lynch RG (1997) Gamma delta T cells of the murine vagina: T cell response in vivo in the absence of the expression of CD2 and CD28 molecules. Int Immunol 9:161–167
Rakasz E, Sandor M, Hagen M, Lynch RG (1996) Activation features of intraepithelial gamma delta Tcells of the murine vagina. Immunol Lett 54:129–134
Witherden DA, Verdino P, Rieder SE, Garijo O, Mills RE, Teyton L, Fischer WH, Wilson IA, Havran WL (2010) The junctional adhesion molecule JAML is a costimulatory receptor for epithelial gammadelta T cell activation. Science 329:1205–1210
Hanrahan CF, Kimpton WG, Howard CJ, Parsons KR, Brandon MR, Andrews AE, Nash AD (1997) Cellular requirements for the activation and proliferation of ruminant gammadelta T cells. J Immunol 159:4287–4294
Koskela K, Arstila TP, Lassila O (1998) Costimulatory function of CD28 in avian gammadelta T cells is evolutionarily conserved. Scand J Immunol 48:635–641
Testi R, Lanier LL (1989) Functional expression of CD28 on T cell antigen receptor gamma/delta-bearing T lymphocytes. Eur J Immunol 19:185–188
Takamizawa M, Fagnoni F, Mehta-Damani A, Rivas A, Engleman EG (1995) Cellular and molecular basis of human gamma delta T cell activation. Role of accessory molecules in alloactivation. J Clin Invest 95:296–303
Lafont V, Liautard J, Gross A, Liautard JP, Favero J (2000) Tumor necrosis factor-alpha production is differently regulated in gamma delta and alpha beta human T lymphocytes. J Biol Chem 275:19282–19287
Penninger JM, Timms E, Shahinian A, Jezo-Bremond A, Nishina H, Ionescu J, Hedrick SM, Mak TW (1995) Alloreactive gamma delta thymocytes utilize distinct costimulatory signals from peripheral T cells. J Immunol 155:3847–3855
Crawford K, Stark A, Kitchens B, Sternheim K, Pantazopoulos V, Triantafellow E, Wang Z, Vasir B, Larsen CE, Gabuzda D et al (2003) CD2 engagement induces dendritic cell activation: implications for immune surveillance and T-cell activation. Blood 102:1745–1752
Tibaldi EV, Salgia R, Reinherz EL (2002) CD2 molecules redistribute to the uropod during T cell scanning: implications for cellular activation and immune surveillance. Proc Natl Acad Sci USA 99:7582–7587
Kaizuka Y, Douglass AD, Vardhana S, Dustin ML, Vale RD (2009) The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells. J Cell Biol 185:521–534
Espagnolle N, Depoil D, Zaru R, Demeur C, Champagne E, Guiraud M, Valitutti S (2007) CD2 and TCR synergize for the activation of phospholipase Cgamma1/calcium pathway at the immunological synapse. Int Immunol 19:239–248
Favier B, Espinosa E, Tabiasco J, Dos Santos C, Bonneville M, Valitutti S, Fournie JJ (2003) Uncoupling between immunological synapse formation and functional outcome in human gamma delta T lymphocytes. J Immunol 171:5027–5033
Pawelec G, Schaudt K, Rehbein A, Olive D, Buhring HJ (1990) Human T cell clones with gamma/delta and alpha/beta receptors are differently stimulated by monoclonal antibodies to CD2. Cell Immunol 129:385–393
Wesselborg S, Janssen O, Pechhold K, Kabelitz D (1991) Selective activation of gamma/delta + T cell clones by single anti-CD2 antibodies. J Exp Med 173:297–304
Lopez RD, Xu S, Guo B, Negrin RS, Waller EK (2000) CD2-mediated IL-12-dependent signals render human gamma delta-T cells resistant to mitogen-induced apoptosis, permitting the large-scale ex vivo expansion of functionally distinct lymphocytes: implications for the development of adoptive immunotherapy strategies. Blood 96:3827–3837
Das H, Sugita M, Brenner MB (2004) Mechanisms of Vdelta1 gammadelta T cell activation by microbial components. J Immunol 172:6578–6586
Budd RC, Russell JQ, van Houten N, Cooper SM, Yagita H, Wolfe J (1992) CD2 expression correlates with proliferative capacity of alpha beta + or gamma delta + CD4-CD8- T cells in lpr mice. J Immunol 148:1055–1064
Van Houten N, Mixter PF, Wolfe J, Budd RC (1993) CD2 expression on murine intestinal intraepithelial lymphocytes is bimodal and defines proliferative capacity. Int Immunol 5:665–672
Simpson TR, Allison JP (2010) Regulation of CD4 T cell activation and effector function by inducible costimulator (ICOS). Curr Opin Immunol 22:326–332
Coyle AJ, Lehar S, Lloyd C, Tian J, Delaney T, Manning S, Nguyen T, Burwell T, Schneider H, Gonzalo JA et al (2000) The CD28-related molecule ICOS is required for effective T cell-dependent immune responses. Immunity 13:95–105
Dong C, Juedes AE, Temann UA, Shresta S, Allison JP, Ruddle NH, Flavell RA (2001) ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409:97–101
Tafuri A, Shahinian A, Bladt F, Yoshinaga SK, Jordana M, Wakeham A, Boucher LM, Bouchard D, Chan VS, Duncan G (2001) ICOS is essential for effective T-helper-cell responses. Nature 409:105–109
Suh WK, Tafuri A, Berg-Brown NN, Shahinian A, Plyte S, Duncan GS, Okada H, Wakeham A, Odermatt B, Ohashi PS et al (2004) The inducible costimulator plays the major costimulatory role in humoral immune responses in the absence of CD28. J Immunol 172:5917–5923
Brandes M, Willimann K, Lang AB, Nam KH, Jin C, Brenner MB, Morita CT, Moser B (2003) Flexible migration program regulates gamma delta T-cell involvement in humoral immunity. Blood 102:3693–3701
Caccamo N, Battistini L, Bonneville M, Poccia F, Fournie JJ, Meraviglia S, Borsellino G, Kroczek RA, La Mendola C, Scotet E et al (2006) CXCR5 identifies a subset of Vgamma9Vdelta2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production. J Immunol 177:5290–5295
Correia DV, d’Orey F, Cardoso BA, Lanca T, Grosso AR, deBarros A, Martins LR, Barata JT, Silva-Santos B (2009) Highly active microbial phosphoantigen induces rapid yet sustained MEK/Erk- and PI-3 K/Akt-mediated signal transduction in anti-tumor human gammadelta T-cells. PLoS One 4:e5657
Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N et al (2001) Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291:319–322
Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC (2010) Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 207:2187–2194
Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher IF, Sander C, Kirkwood JM, Kuchroo V, Zarour HM (2010) Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med 207:2175–2186
Moog-Lutz C, Cave-Riant F, Guibal FC, Breau MA, Di Gioia Y, Couraud PO, Cayre YE, Bourdoulous S, Lutz PG (2003) JAML, a novel protein with characteristics of a junctional adhesion molecule, is induced during differentiation of myeloid leukemia cells. Blood 102:3371–3378
Verdino P, Witherden DA, Havran WL, Wilson IA (2010) The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3 K. Science 329:1210–1214
Hendriks J, Gravestein LA, Tesselaar K, van Lier RA, Schumacher TN, Borst J (2000) CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol 1:433–440
Denoeud J, Moser M (2011) Role of CD27/CD70 pathway of activation in immunity and tolerance. J Leukoc Biol 89:195–203
Hendriks J, Xiao Y, Borst J (2003) CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool. J Exp Med 198:1369–1380
Arens R, Tesselaar K, Baars PA, van Schijndel GM, Hendriks J, Pals ST, Krimpenfort P, Borst J, van Oers MH, van Lier RA (2001) Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNgamma-mediated B cell depletion. Immunity 15:801–812
Arens R, Schepers K, Nolte MA, van Oosterwijk MF, van Lier RA, Schumacher TN, Schumacher TN, van Oers MH (2004) Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. J Exp Med 199:1595–1605
Tesselaar K, Arens R, van Schijndel GM, Baars PA, van der Valk MA, Borst J, van Oers MH, van Lier RA (2003) Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat Immunol 4:49–54
Peperzak V, Xiao Y, Veraar EA, Borst J (2010) CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production. J Clin Invest 120:168–178
Ribot JC, deBarros A, Pang DJ, Neves JF, Peperzak V, Roberts SJ, Girardi M, Borst J, Hayday AC, Pennington DJ et al (2009) CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets. Nat Immunol 10:427–436
Do JS, Fink PJ, Li L, Spolski R, Robinson J, Leonard WJ, Letterio JJ, Min B (2010) Cutting edge: spontaneous development of IL-17-producing gamma delta T cells in the thymus occurs via a TGF-beta 1-dependent mechanism. J Immunol 184:1675–1679
Hayday AC (2009) Gammadelta T cells and the lymphoid stress-surveillance response. Immunity 31:184–196
Shibata K, Yamada H, Nakamura R, Sun X, Itsumi M, Yoshikai Y (2008) Identification of CD25+ gamma delta T cells as fetal thymus-derived naturally occurring IL-17 producers. J Immunol 181:5940–5947
Jensen KD, Su X, Shin S, Li L, Youssef S, Yamasaki S, Steinman L, Saito T, Locksley RM, Davis MM et al (2008) Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma. Immunity 29:90–100
Ribot JC, Chaves-Ferreira M, d’Orey F, Wencker M, Goncalves-Sousa N, Decalf J, Simas JP, Hayday AC, Silva-Santos B (2010) Cutting Edge: Adaptive Versus Innate Receptor Signals Selectively Control the Pool Sizes of Murine IFN-{gamma}- or IL-17-Producing gamma}{delta T Cells upon Infection. J Immunol 185:6421–6425
deBarros A, Chaves-Ferreira M, d’Orey F, Ribot JC, Silva-Santos B (2011) CD70–CD27 interactions provide survival and proliferative signals that regulate T-cell receptor-driven activation of human γδ peripheral blood lymphocytes. Eur J Immunol 41:195–201
Dieli F, Poccia F, Lipp M, Sireci G, Caccamo N, Di Sano C, Salerno A (2003) Differentiation of effector/memory Vdelta2 T cells and migratory routes in lymph nodes or inflammatory sites. J Exp Med 198:391–397
French RR, Taraban VY, Crowther GR, Rowley TF, Gray JC, Johnson PW, Tutt AL, Al-Shamkhani A, Glennie MJ (2007) Eradication of lymphoma by CD8 T cells following anti-CD40 monoclonal antibody therapy is critically dependent on CD27 costimulation. Blood 109:4810–4815
Glouchkova L, Ackermann B, Zibert A, Meisel R, Siepermann M, Janka-Schaub GE, Goebel U, Troeger A, Dilloo D (2009) The CD70/CD27 pathway is critical for stimulation of an effective cytotoxic T cell response against B cell precursor acute lymphoblastic leukemia. J Immunol 182:718–725
Romagnani S, Del Prete G, Maggi E, Chilosi M, Caligaris-Cappio F, Pizzolo G (1995) CD30 and type 2 T helper (Th2) responses. J Leukoc Biol 57:726–730
Tang C, Yamada H, Shibata K, Muta H, Wajjwalku W, Podack ER, Yoshikai Y (2008) A novel role of CD30L/CD30 signaling by T-T cell interaction in Th1 response against mycobacterial infection. J Immunol 181:6316–6327
Sun X, Yamada H, Shibata K, Muta H, Tani K, Podack ER, Yoshikai Y (2010) CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice. J Immunol 185:2222–2230
Ferrarini M, Delfanti F, Gianolini M, Rizzi C, Alfano M, Lazzarin A, Biswas P (2008) NF-kappa B modulates sensitivity to apoptosis, proinflammatory and migratory potential in short- versus long-term cultured human gamma delta lymphocytes. J Immunol 181:5857–5864
Biswas P, Mantelli B, Delfanti F, Ferrarini M, Poli G, Lazzarin A (2003) CD30 ligation differentially affects CXCR4-dependent HIV-1 replication and soluble CD30 secretion in non-Hodgkin cell lines and in gamma delta T lymphocytes. Eur J Immunol 33:3136–3145
Platt RE, Wu KS, Poole K, Newstead CG, Clark B (2009) Soluble CD30 as a prognostic factor for outcome following renal transplantation. J Clin Pathol 62:662–663
Spinozzi F, Agea E, Bistoni O, Forenza N, Monaco A, Falini B, Bassotti G, De Benedictis F, Grignani F, Bertotto A (1995) Local expansion of allergen-specific CD30+ Th2-type gamma delta T cells in bronchial asthma. Mol Med 1:821–826
Biswas P, Rovere P, De Filippi C, Heltai S, Smith C, Dagna L, Poli G, Manfredi AA, Ferrarini M (2000) Engagement of CD30 shapes the secretion of cytokines by human gamma delta T cells. Eur J Immunol 30:2172–2180
Dagna L, Iellem A, Biswas P, Resta D, Tantardini F, Fortis C, Sabbadini MG, D’Ambrosio D, Manfredi AA, Ferrarini M (2002) Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type-1/-2 gamma delta T lymphocytes. Eur J Immunol 32:2934–2943
Sun X, Yamada H, Shibata K, Muta H, Tani K, Podack ER, Iwakura Y, Yoshikai Y (2010) CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses. J Immunol 185:7671–80
Croft M (2010) Control of immunity by the TNFR-related molecule OX40 (CD134). Annu Rev Immunol 28:57–78
Wang C, Lin GH, McPherson AJ, Watts TH (2009) **Immune regulation by 4–1BB and 4–1BBL: complexities and challenges. Immunol Rev 229:192–215
Maniar A, Zhang X, Lin W, Gastman BR, Pauza CD, Strome SE, Chapoval AI (2010) Human gammadelta T lymphocytes induce robust NK cell-mediated antitumor cytotoxicity through CD137 engagement. Blood 116:1726–1733
Shao Z, Schwarz H (2011) CD137 ligand, a member of the tumor necrosis factor family, regulates immune responses via reverse signal transduction. J Leukoc Biol 89:21–9
Eagle RA, Trowsdale J (2007) Promiscuity and the single receptor: NKG2D. Nat Rev Immunol 7:737–744
Gasser S, Orsulic S, Brown EJ, Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190
Champsaur M, Lanier LL (2010) Effect of NKG2D ligand expression on host immune responses. Immunol Rev 235:267–285
Coudert JD, Held W (2006) The role of the NKG2D receptor for tumor immunity. Semin Cancer Biol 16:333–343
Lodoen MB, Lanier LL (2006) Natural killer cells as an initial defense against pathogens. Curr Opin Immunol 18:391–398
Guerra N, Tan YX, Joncker NT, Choy A, Gallardo F, Xiong N, Knoblaugh S, Cado D, Greenberg NM, Raulet DH (2008) NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 28:571–580
Groh V, Rhinehart R, Randolph-Habecker J, Topp MS, Riddell SR, Spies T (2001) Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat Immunol 2:255–260
Das H, Groh V, Kuijl C, Sugita M, Morita CT, Spies T, Bukowski JF (2001) MICA engagement by human Vgamma2Vdelta2 T cells enhances their antigen-dependent effector function. Immunity 15:83–93
Nedellec S, Sabourin C, Bonneville M, Scotet E (2010) NKG2D costimulates human V gamma 9 V delta 2 T cell antitumor cytotoxicity through protein kinase C theta-dependent modulation of early TCR-induced calcium and transduction signals. J Immunol 185:55–63
Rincon-Orozco B, Kunzmann V, Wrobel P, Kabelitz D, Steinle A, Herrmann T (2005) Activation of V gamma 9 V delta 2 T cells by NKG2D. J Immunol 175:2144–2151
Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, Hobby P, Sutton B, Tigelaar RE, Hayday AC (2001) Regulation of cutaneous malignancy by gammadelta T cells. Science 294:605–609
Strid J, Roberts SJ, Filler RB, Lewis JM, Kwong BY, Schpero W, Kaplan DH, Hayday AC, Girardi M (2008) Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis. Nat Immunol 9:146–154
Nitahara A, Shimura H, Ito A, Tomiyama K, Ito M, Kawai K (2006) NKG2D ligation without T cell receptor engagement triggers both cytotoxicity and cytokine production in dendritic epidermal T cells. J Invest Dermatol 126:1052–1058
Wu J, Groh V, Spies T (2002) T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial gamma delta T cells. J Immunol 169:1236–1240
Kong Y, Cao W, Xi X, Ma C, Cui L, He W (2009) The NKG2D ligand ULBP4 binds to TCRgamma9/delta2 and induces cytotoxicity to tumor cells through both TCRgammadelta and NKG2D. Blood 114:310–317
Gomes AQ, Martins DS, Silva-Santos B (2010) Targeting γδ T lymphocytes for cancer immunotherapy: from novel mechanistic insight to clinical application. Cancer Res 70:10024–10027
Gomes AQ, Correia DV, Grosso AR, Lanca T, Ferreira C, Lacerda JF, Barata JT, Silva MG, Silva-Santos B (2010) Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood gammadelta T cells. Haematologica 95:1397–1404
Lanca T, Correia DV, Moita CF, Raquel H, Neves-Costa A, Ferreira C, Ramalho JS, Barata JT, Moita LF, Gomes AQ et al (2010) The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gammadelta T-cell cytotoxicity. Blood 115:2407–2411
Sarrias MR, Gronlund J, Padilla O, Madsen J, Holmskov U, Lozano F (2004) The Scavenger Receptor Cysteine-Rich (SRCR) domain: an ancient and highly conserved protein module of the innate immune system. Crit Rev Immunol 24:1–37
Dalloul A (2009) CD5: a safeguard against autoimmunity and a shield for cancer cells. Autoimmun Rev 8:349–353
Mizoguchi A, Mizoguchi E, de Jong YP, Takedatsu H, Preffer FI, Terhorst C, Bhan AK (2003) Role of the CD5 molecule on TCR gammadelta T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation. Int Immunol 15:97–108
Brown MH, Lacey E (2010) A ligand for CD5 is CD5. J Immunol 185:6068–6074
Liszewski MK, Kemper C, Price JD, Atkinson JP (2005) Emerging roles and new functions of CD46. Springer Semin Immunopathol 27:345–358
Kemper C, Chan AC, Green JM, Brett KA, Murphy KM, Atkinson JP (2003) Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421:388–392
Cardone J, Le Friec G, Vantourout P, Roberts A, Fuchs A, Jackson I, Suddason T, Lord G, Atkinson JP, Cope A et al (2010) Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nat Immunol 11:862–871
Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH (2009) Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity 31:331–341
Petermann F, Rothhammer V, Claussen MC, Haas JD, Blanco LR, Heink S, Prinz I, Hemmer B, Kuchroo VK, Oukka M et al (2010) gammadelta T cells enhance autoimmunity by restraining regulatory T cell responses via an interleukin-23-dependent mechanism. Immunity 33:351–363
Acknowledgments
We thank Richard Lopez and Daniel Olive for their personal communications, and the European Molecular Biology Organisation (Installation Grant, project no. 1440) and Fundação para a Ciência e Tecnologia (PTDC/SAU-MII/ 104158/ 2008) for funding.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
J. C. Ribot and A. de Barros contributed equally to this work.
Rights and permissions
About this article
Cite this article
Ribot, J.C., deBarros, A. & Silva-Santos, B. Searching for “signal 2”: costimulation requirements of γδ T cells. Cell. Mol. Life Sci. 68, 2345–2355 (2011). https://doi.org/10.1007/s00018-011-0698-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00018-011-0698-2