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Activation and Function of Unconventional T Cells

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Book cover Damage-Associated Molecular Patterns in Human Diseases

Abstract

Efferent innate immune responses include the function of unconventional T cells with partial innate properties. While most studies of T lymphocytes have focused on T cells involved in adaptive immune responses by reacting to complexes of peptide and major histocompatibility complex proteins, many other types of T cells do not match this paradigm. As described in this chapter, these cells include CD1-restricted natural killer T cells, MR1-restricted mucosal-associated invariant T cells, and gammadelta T cells. Collectively, these T cells are considered unconventional, in part, because they exert partial innate functions and in part because they can recognize non-classical/non-peptide antigens such as lipids, small-molecule metabolites, and specially modified peptides. Unlike conventional T cells, these unconventional T cells are characterized by semi-invariant, invariant, or even germline-encoded T cell receptors which mediate rapid effector responses. Here, evidence in the perspective of the book is reviewed showing that unconventional T cells are not only activated by recognition of cognate antigens but also—directly or indirectly—by various classes of DAMPs emitted during infectious and sterile injury or exposed by transformed malignant cells. In addition, examples of the various efferent functions of unconventional T cells are briefly addressed pointing to their impressive role in orchestrating and regulating immune responses in infectious and sterile inflammation and tumor surveillance.

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References

  1. Kabelitz D, Peters C, Wesch D, Oberg H-H. Regulatory functions of γδ T cells. Int Immunopharmacol. 2013;16:382–7. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1567576913000398

    Article  CAS  Google Scholar 

  2. Liuzzi AR, McLaren JE, Price DA, Eberl M. Early innate responses to pathogens: pattern recognition by unconventional human T-cells. Curr Opin Immunol. 2015;36:31–7. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0952791515000837

    Article  CAS  Google Scholar 

  3. Hung J-T, Huang J-R, Yu AL. Tailored design of NKT-stimulatory glycolipids for polarization of immune responses. J Biomed Sci. 2017;24:22. Available from: http://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-017-0325-0

    Article  Google Scholar 

  4. Fay NS, Larson EC, Jameson JM. Chronic inflammation and γδ T cells. Front Immunol. 2016;7:210. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27303404

    Article  Google Scholar 

  5. Zou C, Zhao P, Xiao Z, Han X, Fu F, Fu L. γδ T cells in cancer immunotherapy. Oncotarget. 2017;8:8900–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27823972

    PubMed  Google Scholar 

  6. Liuzzi AR, Kift-Morgan A, Lopez-Anton M, Friberg IM, Zhang J, Brook AC, et al. Unconventional human T cells accumulate at the site of infection in response to microbial ligands and induce local tissue remodeling. J Immunol. 2016;197:2195–207. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27527598

    Article  CAS  Google Scholar 

  7. Cerundolo V, Silk JD, Masri SH, Salio M. Harnessing invariant NKT cells in vaccination strategies. Nat Rev Immunol. 2009;9:28–38. Available from: http://www.nature.com/doifinder/10.1038/nri2451

    Article  CAS  Google Scholar 

  8. Grant EP, Degano M, Rosat JP, Stenger S, Modlin RL, Wilson IA, et al. Molecular recognition of lipid antigens by T cell receptors. J Exp Med. 1999;189:195–205. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9874576

    Article  CAS  Google Scholar 

  9. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C, Zhou D, et al. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature. 2005;434:525–9. Available from: http://www.nature.com/doifinder/10.1038/nature03408

    Article  CAS  Google Scholar 

  10. Brennan PJ, Tatituri RVV, Brigl M, Kim EY, Tuli A, Sanderson JP, et al. Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nat Immunol. 2011;12:1202–11. Available from: http://www.nature.com/doifinder/10.1038/ni.2143

    Article  CAS  Google Scholar 

  11. Brigl M, Brenner MB. How invariant natural killer T cells respond to infection by recognizing microbial or endogenous lipid antigens. Semin Immunol. 2010;22:79–86. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1044532309001006

    Article  CAS  Google Scholar 

  12. Kinjo Y, Illarionov P, Vela JL, Pei B, Girardi E, Li X, et al. Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria. Nat Immunol. 2011;12:966–74. Available from: http://www.nature.com/doifinder/10.1038/ni.2096

    Article  CAS  Google Scholar 

  13. Kuylenstierna C, Björkström NK, Andersson SK, Sahlström P, Bosnjak L, Paquin-Proulx D, et al. NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and costimulation of activation by CD1d. Eur J Immunol. 2011;41:1913–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21590763

    Article  CAS  Google Scholar 

  14. Kohlgruber AC, Donado CA, LaMarche NM, Brenner MB, Brennan PJ. Activation strategies for invariant natural killer T cells. Immunogenetics. 2016;68:649–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27457886

    Article  CAS  Google Scholar 

  15. Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB. Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol. 2003;4:1230–7. Available from: http://www.nature.com/doifinder/10.1038/ni1002

    Article  CAS  Google Scholar 

  16. Wang J, Cao X, Zhao J, Zhao H, Wei J, Li Q, et al. Critical roles of conventional dendritic cells in promoting T cell-dependent hepatitis through regulating natural killer T cells. Clin Exp Immunol. 2017;188:127–37. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27891589

    Article  CAS  Google Scholar 

  17. Wei J, Xia S, Sun H, Zhang S, Wang J, Zhao H, et al. Critical role of dendritic cell-derived IL-27 in antitumor immunity through regulating the recruitment and activation of NK and NKT cells. J Immunol. 2013;191:500–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23733881

    Article  CAS  Google Scholar 

  18. Lanier LL. NKG2D receptor and its ligands in host defense. Cancer Immunol Res. 2015;3:575–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26041808

    Article  CAS  Google Scholar 

  19. Matsuda JL, Mallevaey T, Scott-Browne J, Gapin L. CD1d-restricted iNKT cells, the “Swiss-Army knife” of the immune system. Curr Opin Immunol. 2008;20:358–68. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0952791508000435

    Article  CAS  Google Scholar 

  20. Godfrey DI, Rossjohn J. New ways to turn on NKT cells. J Exp Med. 2011;208:1121–5. Available from: http://www.jem.org/lookup/doi/10.1084/jem.20110983

    Article  CAS  Google Scholar 

  21. Bassiri H, Das R, Guan P, Barrett DM, Brennan PJ, Banerjee PP, et al. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo. Cancer Immunol Res. 2014;2:59–69. Available from: http://cancerimmunolres.aacrjournals.org/cgi/doi/10.1158/2326-6066.CIR-13-0104

    Article  CAS  Google Scholar 

  22. Wingender G, Krebs P, Beutler B, Kronenberg M. Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency. J Immunol. 2010;185:2721–9. Available from: http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.1001018

    Article  CAS  Google Scholar 

  23. Crowe NY, Uldrich AP, Kyparissoudis K, Hammond KJL, Hayakawa Y, Sidobre S, et al. Glycolipid antigen drives rapid expansion and sustained cytokine production by NK T cells. J Immunol. 2003;171:4020–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14530322

    Article  CAS  Google Scholar 

  24. Wilson MT, Johansson C, Olivares-Villagómez D, Singh AK, Stanic AK, Wang C-R, et al. The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc Natl Acad Sci U S A. 2003;100:10913–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12960397

    Article  CAS  Google Scholar 

  25. Coquet JM, Chakravarti S, Kyparissoudis K, McNab FW, Pitt LA, McKenzie BS, et al. Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci U S A. 2008;105:11287–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18685112

    Article  CAS  Google Scholar 

  26. Juno JA, Keynan Y, Fowke KR. Invariant NKT cells: regulation and function during viral infection. PLoS Pathog. 2012;8:e1002838. Available from: http://dx.plos.org/10.1371/journal.ppat.1002838

    Article  CAS  Google Scholar 

  27. Tessmer MS, Fatima A, Paget C, Trottein F, Brossay L. NKT cell immune responses to viral infection. Expert Opin Ther Targets. 2009;13:153–62. Available from: http://www.tandfonline.com/doi/full/10.1517/14712590802653601

    Article  CAS  Google Scholar 

  28. Inafuku M, Li C, Kanda Y, Kawamura T, Takeda K, Oku H, et al. Beta-glucosylceramide administration (i.p.) activates natural killer T cells in vivo and prevents tumor metastasis in mice. Lipids. 2012;47:581–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22426862

    Article  CAS  Google Scholar 

  29. Barthelemy A, Ivanov S, Hassane M, Fontaine J, Heurtault B, Frisch B, et al. Exogenous activation of invariant natural killer T cells by α-galactosylceramide reduces pneumococcal outgrowth and dissemination postinfluenza. MBio. 2016;7:e01440–16. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27803187

    Article  CAS  Google Scholar 

  30. Kamaladasa A, Wickramasinghe N, Adikari TN, Gomes L, Shyamali NLA, Salio M, et al. Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection. Clin Exp Immunol. 2016;185:228–38. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26874822

    Article  CAS  Google Scholar 

  31. Artiaga BL, Yang G, Hutchinson TE, Loeb JC, Richt JA, Lednicky JA, et al. Rapid control of pandemic H1N1 influenza by targeting NKT-cells. Sci Rep. 2016;6:37999. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27897246

    Article  CAS  Google Scholar 

  32. Yang J-Q, Zhou Y, Singh RR. Effects of invariant NKT cells on parasite infections and hygiene hypothesis. J Immunol Res. 2016;2016:1–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27563682

    Article  CAS  Google Scholar 

  33. Tian G, Courtney AN, Jena B, Heczey A, Liu D, Marinova E, et al. CD62L+ NKT cells have prolonged persistence and antitumor activity in vivo. J Clin Invest. 2016;126:2341–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27183388

    Article  Google Scholar 

  34. Janakiram NB, Mohammed A, Bryant T, Ritchie R, Stratton N, Jackson L, et al. Loss of natural killer T cells promotes pancreatic cancer in LSL-Kras G12D/+ mice. Immunology. 2017;152(1):36–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28419443

    Article  CAS  Google Scholar 

  35. Gao Y, Williams AP. Role of innate T cells in anti-bacterial immunity. Front Immunol. 2015;6:302. Available from: http://journal.frontiersin.org/Article/10.3389/fimmu.2015.00302/abstract

    Article  Google Scholar 

  36. McEwen-Smith RM, Salio M, Cerundolo V. The regulatory role of invariant NKT cells in tumor immunity. Cancer Immunol Res. 2015;3:425–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25941354

    Article  CAS  Google Scholar 

  37. Vincent MS, Leslie DS, Gumperz JE, Xiong X, Grant EP, Brenner MB. CD1-dependent dendritic cell instruction. Nat Immunol. 2002;3:1163–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12415264

    Article  CAS  Google Scholar 

  38. Brigl M, Brenner MB. CD1: antigen presentation and T cell function. Annu Rev Immunol. 2004;22:817–90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15032598

    Article  CAS  Google Scholar 

  39. Keller CW, Freigang S, Lünemann JD. Reciprocal crosstalk between dendritic cells and natural killer T cells: mechanisms and therapeutic potential. Front Immunol. 2017;8:570. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28596767

    Article  Google Scholar 

  40. Godfrey DI, Uldrich AP, McCluskey J, Rossjohn J, Moody DB. The burgeoning family of unconventional T cells. Nat Immunol. 2015;16:1114–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26482978

    Article  CAS  Google Scholar 

  41. Dasgupta S, Kumar V. Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset. Immunogenetics. 2016;68:665–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27405300

    Article  CAS  Google Scholar 

  42. Jahng A, Maricic I, Aguilera C, Cardell S, Halder RC, Kumar V. Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J Exp Med. 2004;199:947–57. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15051763

    Article  CAS  Google Scholar 

  43. Marrero I, Ware R, Kumar V. Type II NKT cells in inflammation, autoimmunity, microbial immunity, and cancer. Front Immunol. 2015;6:316. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26136748

    Article  Google Scholar 

  44. Tard C, Rouxel O, Lehuen A. Regulatory role of natural killer T cells in diabetes. Biomed J. 2015;38:484–95. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27013448

    Article  Google Scholar 

  45. Speir M, Hermans IF, Weinkove R. Engaging natural killer T cells as “Universal helpers” for vaccination. Drugs. 2017;77:1–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28005229

    Article  CAS  Google Scholar 

  46. Szabo PA, Anantha RV, Shaler CR, McCormick JK, Haeryfar SMM. CD1d- and MR1-restricted T cells in sepsis. Front Immunol. 2015;6:401. Available from: http://journal.frontiersin.org/Article/10.3389/fimmu.2015.00401/abstract

    PubMed  PubMed Central  Google Scholar 

  47. Moreira ML, Tsuji M, Corbett AJ, Araújo MSS, Teixeira-Carvalho A, Martins-Filho OA, et al. MAIT-cells: a tailor-made mate in the ancient battle against infectious diseases? Immunol Lett. 2017;187:53–60. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0165247817300640

    Article  CAS  Google Scholar 

  48. Keller AN, Corbett AJ, Wubben JM, McCluskey J, Rossjohn J. MAIT cells and MR1-antigen recognition. Curr Opin Immunol. 2017;46:66–74. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0952791517300250

    Article  CAS  Google Scholar 

  49. Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. 2012;491:717–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23051753

    Article  CAS  Google Scholar 

  50. Kawachi I, Maldonado J, Strader C, Gilfillan S. MR1-restricted V alpha 19i mucosal-associated invariant T cells are innate T cells in the gut lamina propria that provide a rapid and diverse cytokine response. J Immunol. 2006;176:1618–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16424191

    Article  CAS  Google Scholar 

  51. Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C, et al. Stepwise development of MAIT cells in mouse and human. PLoS Biol. 2009;7:e54. Available from: http://dx.plos.org/10.1371/journal.pbio.1000054

    Article  Google Scholar 

  52. Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M, et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol. 2010;11:701–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20581831

    Article  Google Scholar 

  53. Dusseaux M, Martin E, Serriari N, Péguillet I, Premel V, Louis D, et al. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood. 2011;117:1250–9. Available from: http://www.bloodjournal.org/cgi/doi/10.1182/blood-2010-08-303,339

    Article  CAS  Google Scholar 

  54. Brozova J, Karlova I, Novak J. Analysis of the phenotype and function of the subpopulations of mucosal-associated invariant T cells. Scand J Immunol. 2016;84:245–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27474379

    Article  CAS  Google Scholar 

  55. Tang X-Z, Jo J, Tan AT, Sandalova E, Chia A, Tan KC, et al. IL-7 licenses activation of human liver intrasinusoidal mucosal-associated invariant T cells. J Immunol. 2013;190:3142–52. Available from: http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.1203218

    Article  CAS  Google Scholar 

  56. Chen Z, Wang H, D’Souza C, Sun S, Kostenko L, Eckle SBG, et al. Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals. Mucosal Immunol. 2017;10:58–68. Available from: http://www.nature.com/doifinder/10.1038/mi.2016.39

    Article  CAS  Google Scholar 

  57. Chiba A, Tajima R, Tomi C, Miyazaki Y, Yamamura T, Miyake S. Mucosal-associated invariant T cells promote inflammation and exacerbate disease in murine models of arthritis. Arthritis Rheum. 2012;64:153–61. Available from: http://doi.wiley.com/10.1002/art.33314

    Article  CAS  Google Scholar 

  58. Ussher JE, Bilton M, Attwod E, Shadwell J, Richardson R, de Lara C, et al. CD161++ CD8+ T cells, including the MAIT cell subset, are specifically activated by IL-12 + IL-18 in a TCR-independent manner. Eur J Immunol. 2014;44:195–203. Available from: http://doi.wiley.com/10.1002/eji.201343509

    Article  CAS  Google Scholar 

  59. Willing A, Leach OA, Ufer F, Attfield KE, Steinbach K, Kursawe N, et al. CD8+ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis. Eur J Immunol. 2014;44:3119–28. Available from: http://doi.wiley.com/10.1002/eji.201344160

    Article  CAS  Google Scholar 

  60. van Wilgenburg B, Scherwitzl I, Hutchinson EC, Leng T, Kurioka A, Kulicke C, et al. MAIT cells are activated during human viral infections. Nat Commun. 2016;7:11653. Available from: http://www.nature.com/doifinder/10.1038/ncomms11653

    Article  Google Scholar 

  61. Georgel P, Radosavljevic M, Macquin C, Bahram S. The non-conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice. Mol Immunol. 2011;48:769–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21190736

    Article  CAS  Google Scholar 

  62. Kurioka A, Ussher JE, Cosgrove C, Clough C, Fergusson JR, Smith K, et al. MAIT cells are licensed through granzyme exchange to kill bacterially sensitized targets. Mucosal Immunol. 2015;8:429–40. Available from: http://www.nature.com/doifinder/10.1038/mi.2014.81

    Article  CAS  Google Scholar 

  63. Le Bourhis L, Guerri L, Dusseaux M, Martin E, Soudais C, Lantz O. Mucosal-associated invariant T cells: unconventional development and function. Trends Immunol. 2011;32:212–8. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1471490611000408

    Article  Google Scholar 

  64. Turtle CJ, Delrow J, Joslyn RC, Swanson HM, Basom R, Tabellini L, et al. Innate signals overcome acquired TCR signaling pathway regulation and govern the fate of human CD161(hi) CD8α+ semi-invariant T cells. Blood. 2011;118:2752–62. Available from: http://www.bloodjournal.org/cgi/doi/10.1182/blood-2011-02-334,698

    Article  CAS  Google Scholar 

  65. Sattler A, Dang-Heine C, Reinke P, Babel N. IL-15 dependent induction of IL-18 secretion as a feedback mechanism controlling human MAIT-cell effector functions. Eur J Immunol. 2015;45:2286–98. Available from: http://doi.wiley.com/10.1002/eji.201445313

    Article  CAS  Google Scholar 

  66. Bianchini E, De Biasi S, Simone AM, Ferraro D, Sola P, Cossarizza A, et al. Invariant natural killer T cells and mucosal-associated invariant T cells in multiple sclerosis. Immunol Lett. 2017;183:1–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28119072

    Article  CAS  Google Scholar 

  67. Adams EJ, Gu S, Luoma AM. Human gamma delta T cells: evolution and ligand recognition. Cell Immunol. 2015;296:31–40. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0008874915000945

    Article  CAS  Google Scholar 

  68. Chien Y, Meyer C, Bonneville M. γδ T cells: first line of defense and beyond. Annu Rev Immunol. 2014;32:121–55. Available from: http://www.annualreviews.org/doi/10.1146/annurev-immunol-032713-120,216

    Article  CAS  Google Scholar 

  69. Kabelitz D, Déchanet-Merville J. Editorial: “Recent advances in gamma/delta T cell biology: new ligands, new functions, and new translational perspectives”. Front Immunol. 2015;6:371. Available from: http://journal.frontiersin.org/Article/10.3389/fimmu.2015.00371/abstract

    Article  Google Scholar 

  70. Ribeiro ST, Ribot JC, Silva-Santos B. Five layers of receptor signaling in γδ T-cell differentiation and activation. Front Immunol. 2015;6:15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25674089

    Article  Google Scholar 

  71. Domae E, Hirai Y, Ikeo T, Goda S, Shimizu Y. Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells. Oncotarget. 2017;8(28):45928–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28521284

    Article  Google Scholar 

  72. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479–89. Available from: http://www.nature.com/doifinder/10.1038/nri2800

    Article  CAS  Google Scholar 

  73. Vantourout P, Hayday A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nat Rev Immunol. 2013;13:88–100. Available from: http://www.nature.com/doifinder/10.1038/nri3384

    Article  CAS  Google Scholar 

  74. Papotto PH, Ribot JC, Silva-Santos B. IL-17(+) γδ T cells as kick-starters of inflammation. Nat Immunol. 2017;18:604–11. Available from: http://www.nature.com/doifinder/10.1038/ni.3726

    Article  CAS  Google Scholar 

  75. Lalor SJ, McLoughlin RM. Memory γδ T cells-newly appreciated protagonists in infection and immunity. Trends Immunol. 2016;37:690–702. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1471490616300886

    Article  CAS  Google Scholar 

  76. Caccamo N, La Mendola C, Orlando V, Meraviglia S, Todaro M, Stassi G, et al. Differentiation, phenotype, and function of interleukin-17-producing human Vγ9Vδ2 T cells. Blood. 2011;118:129–38. Available from: http://www.bloodjournal.org/cgi/doi/10.1182/blood-2011-01-331,298

    Article  CAS  Google Scholar 

  77. Silva-Santos B. γδ cells making IL-17. Blood. 2011;118:3–5. Available from: http://www.bloodjournal.org/cgi/doi/10.1182/blood-2011-05-351,726

    Article  CAS  Google Scholar 

  78. Khairallah C, Déchanet-Merville J, Capone M. γδ T cell-mediated immunity to cytomegalovirus infection. Front Immunol. 2017;8:105. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28232834

    Article  Google Scholar 

  79. Cimini E, Viola D, Cabeza-Cabrerizo M, Romanelli A, Tumino N, Sacchi A, et al. Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections. PLoS Negl Trop Dis. 2017;11:e0005645. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28558022

    Article  Google Scholar 

  80. Lança T, Silva-Santos B. The split nature of tumor-infiltrating leukocytes: implications for cancer surveillance and immunotherapy. Oncoimmunology. 2012;1:717–25. Available from: http://www.tandfonline.com/doi/abs/10.4161/onci.20068

    Article  Google Scholar 

  81. Rincon-Orozco B, Kunzmann V, Wrobel P, Kabelitz D, Steinle A, Herrmann T. Activation of V gamma 9 V delta 2 T cells by NKG2D. J Immunol. 2005;175:2144–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16081780

    Article  CAS  Google Scholar 

  82. Rei M, Pennington DJ, Silva-Santos B. The emerging protumor role of γδ T lymphocytes: implications for cancer immunotherapy. Cancer Res. 2015;75:798–802. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25660949

    Article  CAS  Google Scholar 

  83. Cheng M, Hu S. Lung-resident γδ T cells and their roles in lung diseases. Immunology. 2017;151(4):375–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28555812

    Article  CAS  Google Scholar 

  84. Hasan MS, Bergmeier LA, Petrushkin H, Fortune F. Gamma delta (γδ) T cells and their involvement in Behçet’s disease. J Immunol Res. 2015;2015:1–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26539557

    Article  Google Scholar 

  85. Van Acker HH, Anguille S, Van Tendeloo VF, Lion E. Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy. Oncoimmunology. 2015;4:e1021538. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26405575

    Article  Google Scholar 

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Land, W.G. (2018). Activation and Function of Unconventional T Cells. In: Damage-Associated Molecular Patterns in Human Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-78655-1_28

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