The emerging roles of gamma-delta T cells in tissue inflammation in experimental autoimmune encephalomyelitis

Frontiers in Immunology

Volumn 7, Issue JAN, 2016, Pages

  Malik, Sakshi ^a   Want, Muzamil Yaqub ^a   Awasthi, Amit ^a  

^a TRANSLATIONAL HEALTH SCIENCE AND TECHNOLOGY INSTITUTE   (India)

Author keywords

Autoimmunity; Cytokines; Gamma Delta T cells; Inflammation; Th17 cells

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 17; INTERLEUKIN 18; INTERLEUKIN 23; INTERLEUKIN 4;

CELL DIFFERENTIATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GAMMA DELTA T LYMPHOCYTE; GENETIC MANIPULATION; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; MULTIPLE SCLEROSIS; NONHUMAN; PATHOGENESIS; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVIEW; TISSUE INJURY;

EID: 84958154941     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2016.00014     Document Type: Review

References (92)

1. Carding SR, Egan PJ. Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol (2002) 2:336-45. doi:10.1038/nri797
2. Saito H, Kranz DM, Takagaki Y, Hayday AC, Eisen HN, Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature (1984) 309:757-62. doi:10.1038/309757a0
3. Brenner MB, McLean J, Dialynas DP, Strominger JL, Smith JA, Owen FL, et al. Identification of a putative second T-cell receptor. Nature (1986) 322:145-9. doi:10.1038/322145a0
4. Born WK, Jin N, Aydintug MK, Wands JM, French JD, Roark CL, et al. Gammadelta T lymphocytes-selectable cells within the innate system? J Clin Immunol (2007) 27:133-44. doi:10.1007/s10875-007-9077-z
5. O'Brien RL, Roark CL, Jin N, Aydintug MK, French JD, Chain JL, et al. Gammadelta T-cell receptors: functional correlations. Immunol Rev (2007) 215:77-88. doi:10.1111/j.1600-065X.2006.00477.x
6. Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M. Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity (2009) 31:321-30. doi:10.1016/j.immuni.2009.06.020
7. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity (2009) 31:331-41. doi:10.1016/j.immuni.2009.08.001
8. Petermann F, Rothhammer V, Claussen MC, Haas JD, Blanco LR, Heink S, et al. Gammadelta T cells enhance autoimmunity by restraining regulatory T cell responses via an interleukin-23-dependent mechanism. Immunity (2010) 33:351-63. doi:10.1016/j.immuni.2010.08.013
9. Lalor SJ, Dungan LS, Sutton CE, Basdeo SA, Fletcher JM, Mills KH. Caspase-1-processed cytokines IL-1beta and IL-18 promote IL-17 production by gammadelta and CD4 T cells that mediate autoimmunity. J Immunol (2011) 186:5738-48. doi:10.4049/jimmunol.1003597
10. Lukens JR, Barr MJ, Chaplin DD, Chi H, Kanneganti TD. Inflammasome-derived IL-1beta regulates the production of GM-CSF by CD4(+) T cells and gammadelta T cells. J Immunol (2012) 188:3107-15. doi:10.4049/jimmunol.1103308
11. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol (2009) 27:485-517. doi:10.1146/annurev.immunol.021908.132710
12. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell (2006) 126:1121-33. doi:10.1016/j.cell.2006.07.035
13. Awasthi A, Riol-Blanco L, Jager A, Korn T, Pot C, Galileos G, et al. Cutting edge: IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells. J Immunol (2009) 182:5904-8. doi:10.4049/jimmunol.0900732
14. Nunez C, Dema B, Cenit MC, Polanco I, Maluenda C, Arroyo R, et al. IL23R: a susceptibility locus for celiac disease and multiple sclerosis? Genes Immun (2008) 9:289-93. doi:10.1038/gene.2008.16
15. Blink SE, Miller SD. The contribution of gammadelta T cells to the pathogenesis of EAE and MS. Curr Mol Med (2009) 9:15-22. doi:10.2174/156652409787314516
16. Paul S, Shilpi S, Lal G. Role of gamma-delta (gammadelta) T cells in autoimmunity. J Leukoc Biol (2015) 97:259-71. doi:10.1189/jlb.3RU0914-443R
17. Chien YH, Konigshofer Y. Antigen recognition by gammadelta T cells. Immunol Rev (2007) 215:46-58. doi:10.1111/j.1600-065X.2006.00470.x
18. Konigshofer Y, Chien YH. Gammadelta T cells-innate immune lymphocytes? Curr Opin Immunol (2006) 18:527-33. doi:10.1016/j.coi.2006.07.008
19. Correa I, Bix M, Liao NS, Zijlstra M, Jaenisch R, Raulet D. Most gamma delta T cells develop normally in beta 2-microglobulin-deficient mice. Proc Natl Acad Sci U S A (1992) 89:653-7. doi:10.1073/pnas.89.2.653
20. Bigby M, Markowitz JS, Bleicher PA, Grusby MJ, Simha S, Siebrecht M, et al. Most gamma delta T cells develop normally in the absence of MHC class II molecules. J Immunol (1993) 151:4465-75.
21. Crowley MP, Reich Z, Mavaddat N, Altman JD, Chien Y. The recognition of the nonclassical major histocompatibility complex (MHC) class I molecule, T10, by the gammadelta T cell, G8. J Exp Med (1997) 185:1223-30. doi:10.1084/jem.185.7.1223
22. Crowley MP, Fahrer AM, Baumgarth N, Hampl J, Gutgemann I, Teyton L, et al. A population of murine gammadelta T cells that recognize an inducible MHC class Ib molecule. Science (2000) 287:314-6. doi:10.1126/science.287.5451.314
23. Wu J, Groh V, Spies T. 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 (2002) 169:1236-40. doi:10.4049/jimmunol.169.3.1236
24. Haas W, Pereira P, Tonegawa S. Gamma/delta cells. Annu Rev Immunol (1993) 11:637-85. doi:10.1146/annurev.iy.11.040193.003225
25. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science (1999) 285:727-9. doi:10.1126/science.285.5428.727
26. Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H. Differential production of interferon-gamma and interleukin-4 in response to Th1-and Th2-stimulating pathogens by gamma delta T cells in vivo. Nature (1995) 373:255-7. doi:10.1038/373255a0
27. Riol-Blanco L, Lazarevic V, Awasthi A, Mitsdoerffer M, Wilson BS, Croxford A, et al. IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections. J Immunol (2010) 184:1710-20. doi:10.4049/jimmunol.0902796
28. Olive C. Gamma delta T cell receptor variable region usage during the development of experimental allergic encephalomyelitis. J Neuroimmunol (1995) 62:1-7. doi:10.1016/0165-5728(95)00081-C
29. Olive C. T cell receptor usage in autoimmune disease. Immunol Cell Biol (1995) 73:297-307. doi:10.1038/icb.1995.46
30. Ponomarev ED, Novikova M, Yassai M, Szczepanik M, Gorski J, Dittel BN. Gamma delta T cell regulation of IFN-gamma production by central nervous system-infiltrating encephalitogenic T cells: correlation with recovery from experimental autoimmune encephalomyelitis. J Immunol (2004) 173:1587-95. doi:10.4049/jimmunol.173.3.1587
31. Reynolds JM, Martinez GJ, Chung Y, Dong C. Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation. Proc Natl Acad Sci U S A (2012) 109:13064-9. doi:10.1073/pnas.1120585109
32. Hirsh MI, Junger WG. Roles of heat shock proteins and gamma delta T cells in inflammation. Am J Respir Cell Mol Biol (2008) 39:509-13. doi:10.1165/rcmb.2008-0090TR
33. Roark CL, Simonian PL, Fontenot AP, Born WK, O'Brien RL. Gammadelta T cells: an important source of IL-17. Curr Opin Immunol (2008) 20:353-7. doi:10.1016/j.coi.2008.03.006
34. Blink SE, Caldis MW, Goings GE, Harp CT, Malissen B, Prinz I, et al. Gammadelta T cell subsets play opposing roles in regulating experimental autoimmune encephalomyelitis. Cell Immunol (2014) 290:39-51. doi:10.1016/j.cellimm.2014.04.013
35. Roark CL, French JD, Taylor MA, Bendele AM, Born WK, O'Brien RL. Exacerbation of collagen-induced arthritis by oligoclonal, IL-17-producing gamma delta T cells. J Immunol (2007) 179:5576-83. doi:10.4049/jimmunol.179.8.5576
36. Ribot JC, deBarros A, Pang DJ, Neves JF, Peperzak V, Roberts SJ, et al. CD27 is a thymic determinant of the balance between interferon-gamma-and interleukin 17-producing gammadelta T cell subsets. Nat Immunol (2009) 10:427-36. doi:10.1038/ni.1717
37. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature (2003) 421:744-8. doi:10.1038/nature01355
38. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity (2008) 28:445-53. doi:10.1016/j.immuni.2008.03.001
39. Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, et al. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol (1996) 156:5-7.
40. Duhen R, Glatigny S, Arbelaez CA, Blair TC, Oukka M, Bettelli E. Cutting edge: the pathogenicity of IFN-gamma-producing Th17 cells is independent of T-bet. J Immunol (2013) 190:4478-82. doi:10.4049/jimmunol.1203172
41. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector Th17 and regulatory T cells. Nature (2006) 441:235-8. doi:10.1038/nature04753
42. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity (2006) 24:179-89. doi:10.1016/j.immuni.2006.01.001
43. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature (2006) 441:231-4. doi:10.1038/nature04754
44. Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol (2007) 8:967-74. doi:10.1038/ni1488
45. Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature (2007) 448:484-7. doi:10.1038/nature05970
46. Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature (2007) 448:480-3. doi:10.1038/nature05969
47. Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol (2006) 177:566-73. doi:10.4049/jimmunol.177.1.566
48. Do JS, Fink PJ, Li L, Spolski R, Robinson J, Leonard WJ, et al. 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 (2010) 184:1675-9. doi:10.4049/jimmunol.0903539
49. Spahn TW, Issazadah S, Salvin AJ, Weiner HL. Decreased severity of myelin oligodendrocyte glycoprotein peptide 33-35-induced experimental autoimmune encephalomyelitis in mice with a disrupted TCR delta chain gene. Eur J Immunol (1999) 29:4060-71. doi:10.1002/(SICI)1521-4141(199912)29:12<4060::AID-IMMU4060>3.0.CO;2-S
50. Rajan AJ, Klein JD, Brosnan CF. The effect of gammadelta T cell depletion on cytokine gene expression in experimental allergic encephalomyelitis. J Immunol (1998) 160:5955-62.
51. Odyniec A, Szczepanik M, Mycko MP, Stasiolek M, Raine CS, Selmaj KW. Gammadelta T cells enhance the expression of experimental autoimmune encephalomyelitis by promoting antigen presentation and IL-12 production. J Immunol (2004) 173:682-94. doi:10.4049/jimmunol.173.1.682
52. Rajan AJ, Gao YL, Raine CS, Brosnan CF. A pathogenic role for gamma delta T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse. J Immunol (1996) 157:941-9.
53. Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med (2007) 13:423-31. doi:10.1038/nm1564
54. Lockhart E, Green AM, Flynn JL. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol (2006) 177:4662-9. doi:10.4049/jimmunol.177.7.4662
55. Umemura M, Kawabe T, Shudo K, Kidoya H, Fukui M, Asano M, et al. Involvement of IL-17 in Fas ligand-induced inflammation. Int Immunol (2004) 16:1099-108. doi:10.1093/intimm/dxh111
56. Umemura M, Yahagi A, Hamada S, Begum MD, Watanabe H, Kawakami K, et al. IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol (2007) 178:3786-96. doi:10.4049/jimmunol.178.6.3786
57. Shibata K, Yamada H, Hara H, Kishihara K, Yoshikai Y. Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production. J Immunol (2007) 178:4466-72. doi:10.4049/jimmunol.178.7.4466
58. Kuchroo VK, Anderson AC, Waldner H, Munder M, Bettelli E, Nicholson LB. T cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire. Annu Rev Immunol (2002) 20:101-23. doi:10.1146/annurev.immunol.20.081701.141316
59. Lees JR, Iwakura Y, Russell JH. Host T cells are the main producers of IL-17 within the central nervous system during initiation of experimental autoimmune encephalomyelitis induced by adoptive transfer of Th1 cell lines. J Immunol (2008) 180:8066-72. doi:10.4049/jimmunol.180.12.8066
60. Smith SS, Barnum SR. Differential expression of beta 2-integrins and cytokine production between gammadelta and alphabeta T cells in experimental autoimmune encephalomyelitis. J Leukoc Biol (2008) 83:71-9. doi:10.1189/jlb.0407263
61. Wohler JE, Smith SS, Zinn KR, Bullard DC, Barnum SR. Gammadelta T cells in EAE: early trafficking events and cytokine requirements. Eur J Immunol (2009) 39:1516-26. doi:10.1002/eji.200839176
62. Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med (2006) 203:1685-91. doi:10.1084/jem.20060285
63. Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity (2007) 26:371-81. doi:10.1016/j.immuni.2007.02.009
64. Shibata K, Yamada H, Nakamura R, Sun X, Itsumi M, Yoshikai Y. Identification of CD25+ gamma delta T cells as fetal thymus-derived naturally occurring IL-17 producers. J Immunol (2008) 181:5940-7. doi:10.4049/jimmunol.181.9.5940
65. Wang X, Wei Y, Liu X, Xing C, Han G, Chen G, et al. IL-15-secreting gammadeltaT cells induce memory T cells in experimental allergic encephalomyelitis (EAE) mice. Mol Immunol (2015) 66:402-8. doi:10.1016/j.molimm.2015.04.021
66. Shi FD, Takeda K, Akira S, Sarvetnick N, Ljunggren HG. IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-gamma by NK cells. J Immunol (2000) 165:3099-104. doi:10.4049/jimmunol.165.6.3099
67. Gutcher I, Urich E, Wolter K, Prinz M, Becher B. Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation. Nat Immunol (2006) 7:946-53. doi:10.1038/ni1377
68. Shi Y, Liu CH, Roberts AI, Das J, Xu G, Ren G, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know. Cell Res (2006) 16:126-33. doi:10.1038/sj.cr.7310017
69. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1-and IL-23-induced production of the cytokine GM-CSF. Nat Immunol (2011) 12:568-75. doi:10.1038/ni.2031
70. Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN. GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol (2007) 178:39-48. doi:10.4049/jimmunol.178.1.39
71. Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol (2011) 12:560-7. doi:10.1038/ni.2027
72. Croxford AL, Lanzinger M, Hartmann FJ, Schreiner B, Mair F, Pelczar P, et al. The cytokine GM-CSF drives the inflammatory signature of CCR2 monocytes and licenses autoimmunity. Immunity (2015) 43:502-14. doi:10.1016/j.immuni.2015.08.010
73. Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev (2011) 241:260-8. doi:10.1111/j.1600-065X.2011.01018.x
74. Ramsdell F, Ziegler SF. FOXP3 and scurfy: how it all began. Nat Rev Immunol (2014) 14:343-9. doi:10.1038/nri3650
75. Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol (2007) 8:191-7. doi:10.1038/ni1428
76. Korn T, Mitsdoerffer M, Croxford AL, Awasthi A, Dardalhon VA, Galileos G, et al. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A (2008) 105:18460-5. doi:10.1073/pnas.0809850105
77. Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, et al. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol (2007) 8:1380-9. doi:10.1038/ni1541
78. Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science (2003) 299:1033-6. doi:10.1126/science.1078231
79. Izcue A, Hue S, Buonocore S, Arancibia-Carcamo CV, Ahern PP, Iwakura Y, et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity (2008) 28:559-70. doi:10.1016/j.immuni.2008.02.019
80. Kobayashi Y, Kawai K, Ito K, Honda H, Sobue G, Yoshikai Y. Aggravation of murine experimental allergic encephalomyelitis by administration of T-cell receptor gammadelta-specific antibody. J Neuroimmunol (1997) 73:169-74. doi:10.1016/S0165-5728(96)00187-7
81. Ponomarev ED, Dittel BN. Gamma delta T cells regulate the extent and duration of inflammation in the central nervous system by a Fas ligand-dependent mechanism. J Immunol (2005) 174:4678-87. doi:10.4049/jimmunol.174.8.4678
82. Koenecke C, Chennupati V, Schmitz S, Malissen B, Forster R, Prinz I. In vivo application of mAb directed against the gammadelta TCR does not deplete but generates "invisible" gammadelta T cells. Eur J Immunol (2009) 39:372-9. doi:10.1002/eji.200838741
83. Welte T, Lamb J, Anderson JF, Born WK, O'Brien RL, Wang T. Role of two distinct gammadelta T cell subsets during West Nile virus infection. FEMS Immunol Med Microbiol (2008) 53:275-83. doi:10.1111/j.1574-695X.2008.00430.x
84. Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, et al. Regulation of cutaneous malignancy by gammadelta T cells. Science (2001) 294:605-9. doi:10.1126/science.1063916
85. Jameson J, Havran WL. Skin gammadelta T-cell functions in homeostasis and wound healing. Immunol Rev (2007) 215:114-22. doi:10.1111/j.1600-065X.2006.00483.x
86. Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R. Protection of the intestinal mucosa by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A (2002) 99:14338-43. doi:10.1073/pnas.212290499
87. Tsuchiya T, Fukuda S, Hamada H, Nakamura A, Kohama Y, Ishikawa H, et al. Role of gamma delta T cells in the inflammatory response of experimental colitis mice. J Immunol (2003) 171:5507-13. doi:10.4049/jimmunol.171.10.5507
88. Dandekar AA, Perlman S. Virus-induced demyelination in nude mice is mediated by gamma delta T cells. Am J Pathol (2002) 161:1255-63. doi:10.1016/S0002-9440(10)64402-1
89. Furlan R, Martino G, Galbiati F, Poliani PL, Smiroldo S, Bergami A, et al. Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. J Immunol (1999) 163:2403-9.
90. Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA. Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sci U S A (1992) 89:4588-92. doi:10.1073/pnas.89.10.4588
91. Hvas J, Oksenberg JR, Fernando R, Steinman L, Bernard CC. Gamma delta T cell receptor repertoire in brain lesions of patients with multiple sclerosis. J Neuroimmunol (1993) 46:225-34. doi:10.1016/0165-5728(93)90253-U
92. Korn T, Petermann F. Development and function of interleukin 17-producing gammadelta T cells. Ann N Y Acad Sci (2012) 1247:34-45. doi:10.1111/j.1749-6632.2011.06355.x