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Published in: Arthritis Research & Therapy 5/2003

Open Access 01-10-2003 | Research article

Vγ9/Vδ2 T lymphocytes in Italian patients with Behçet's disease - evidence for expansion, and tumour necrosis factor receptor II and interleukin-12 receptor β1 expression in active disease

Authors: Giovanni Triolo, Antonina Accardo-Palumbo, Francesco Dieli, Francesco Ciccia, Angelo Ferrante, Ennio Giardina, Caterina Di Sano, Giuseppe Licata

Published in: Arthritis Research & Therapy | Issue 5/2003

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Abstract

Behçet's disease is a multisystem disease in which there is evidence of immunological dysregulation. It has been proposed that γ/δ T cells are involved in its pathogenesis. The aim of the present study was to assess the capacity of γ/δ T cells with phenotype Vγ9/Vδ2, from a group of Italian patients with Behçet's disease, to proliferate in the presence of various phosphoantigens and to express tumour necrosis factor (TNF) and IL-12 receptors. Twenty-five patients and 45 healthy individuals were studied. Vγ9/Vδ2 T cells were analyzed by fluorescence activated cell sorting, utilizing specific monoclonal antibodies. For the expansion of Vγ9/Vδ2 T cells, lymphocytes were cultured in the presence of various phosphoantigens. The expression of TNF receptor II and IL-12 receptor β1 was evaluated with the simultaneous use of anti-TNF receptor II phycoerythrin-labelled (PE) or anti-IL-12 receptor β1 PE and anti-Vδ2 T-cell receptor fluorescein isothiocyanate. There was a certain hierarchy in the response of Vγ9/Vδ2 T cells toward the different phosphoantigens, with the highest expansion factor obtained with dimethylallyl pyrophosphate and the lowest with xylose 1P. The expansion factor was fivefold greater in patients with active disease than in those with inactive disease or in control individuals. TNF receptor II and IL-12 receptor β1 expressions were increased in both patients and control individuals. The proportion of Vγ9/Vδ2 T cells bearing these receptors was raised in active disease when Vγ9/Vδ2 T cells were cultured in the presence of dimethylallyl pyrophosphate. These results indicate that Vγ9/Vδ2 T cell activation is correlated with disease progression and probably involved in the pathogenesis.
Literature
1.
go back to reference Mizuki N, Inoko H, Ando H, Nakamura S, Kashiwase K, Akara T, Fujino Y, Masuda K, Takiguchi M, Ohno S: Behçet's disease associated with one of theHLA-B51 subantigens, HLA-B*5101. Am J Ophthalmol. 1993, 116: 406-409.CrossRefPubMed Mizuki N, Inoko H, Ando H, Nakamura S, Kashiwase K, Akara T, Fujino Y, Masuda K, Takiguchi M, Ohno S: Behçet's disease associated with one of theHLA-B51 subantigens, HLA-B*5101. Am J Ophthalmol. 1993, 116: 406-409.CrossRefPubMed
2.
go back to reference Takeno M, Kaiyone A, Yamashita N, Takiguchi M, Mizushima Y, Kaneoka H, Sakane T: Excessive function of peripheral blood neutrophils from patients with Behçet's disease and from HLA-B51 transgenic mice. Arthritis Rheum. 1995, 38: 426-433.CrossRefPubMed Takeno M, Kaiyone A, Yamashita N, Takiguchi M, Mizushima Y, Kaneoka H, Sakane T: Excessive function of peripheral blood neutrophils from patients with Behçet's disease and from HLA-B51 transgenic mice. Arthritis Rheum. 1995, 38: 426-433.CrossRefPubMed
3.
go back to reference Sakane T, Kotani H, Takada S, Tsunematsu T: Functional aberration of T cell subsets in patients with Behçet's disease. Arthritis Rheum. 1982, 25: 1343-1351.CrossRefPubMed Sakane T, Kotani H, Takada S, Tsunematsu T: Functional aberration of T cell subsets in patients with Behçet's disease. Arthritis Rheum. 1982, 25: 1343-1351.CrossRefPubMed
4.
go back to reference Emmi L, Salvati G, Brugnolo F, Marchione T: Immunopathological aspects of Behçet's disease. Clin Exp Rheumatol. 1995, 13: 687-691.PubMed Emmi L, Salvati G, Brugnolo F, Marchione T: Immunopathological aspects of Behçet's disease. Clin Exp Rheumatol. 1995, 13: 687-691.PubMed
5.
go back to reference Triolo G, Accardo-Palumbo A, Triolo G, Carbone MC, Ferrante A, Giardina E: Enhancement of endothelial cell E-selectin expression by sera from patients with active Behçet's disease: moderate correlation with anti-endothelial cell antibodies and myeloperoxidase levels. Clin Immunol. 1999, 91: 330-337. 10.1006/clim.1999.4687.CrossRefPubMed Triolo G, Accardo-Palumbo A, Triolo G, Carbone MC, Ferrante A, Giardina E: Enhancement of endothelial cell E-selectin expression by sera from patients with active Behçet's disease: moderate correlation with anti-endothelial cell antibodies and myeloperoxidase levels. Clin Immunol. 1999, 91: 330-337. 10.1006/clim.1999.4687.CrossRefPubMed
6.
go back to reference Accardo-Palumbo A, Triolo G, Carbone MC, Ferrante A, Ciccia F, Giardina E, Triolo G: Polymorphonuclear leukocyte myeloperoxidase levels in patients with Behçet's disease. Clin Exp Rheumatol. 2000, 18: 495-498.PubMed Accardo-Palumbo A, Triolo G, Carbone MC, Ferrante A, Ciccia F, Giardina E, Triolo G: Polymorphonuclear leukocyte myeloperoxidase levels in patients with Behçet's disease. Clin Exp Rheumatol. 2000, 18: 495-498.PubMed
7.
go back to reference Gul A, Esin S, Dilsen N, Konice E, Wigzell H, Biberfeld P: Immunohistology of skin pathergy reaction in Behçet's disease. Br J Dermatol. 1995, 132: 901-907.CrossRefPubMed Gul A, Esin S, Dilsen N, Konice E, Wigzell H, Biberfeld P: Immunohistology of skin pathergy reaction in Behçet's disease. Br J Dermatol. 1995, 132: 901-907.CrossRefPubMed
8.
go back to reference Chateris DG, Barton K, McCarthy AC, Lightman SL: CD4 + lymphocyte involvement in ocular Behçet's disease. Autoimmunity. 1992, 12: 201-206.CrossRef Chateris DG, Barton K, McCarthy AC, Lightman SL: CD4 + lymphocyte involvement in ocular Behçet's disease. Autoimmunity. 1992, 12: 201-206.CrossRef
9.
go back to reference Fortune F, Walker J, Lehner T: The expression of γ/δ T cell receptor and the prevalence of primed, activated and IgA-bound T cells in Behçet's syndrome. Clin Exp Immunol. 1990, 82: 326-332.PubMedCentralCrossRefPubMed Fortune F, Walker J, Lehner T: The expression of γ/δ T cell receptor and the prevalence of primed, activated and IgA-bound T cells in Behçet's syndrome. Clin Exp Immunol. 1990, 82: 326-332.PubMedCentralCrossRefPubMed
10.
go back to reference Komano H, Fujiura Y, Kawaguchi M, Matsumoto S, Hashimoto Y, Obana S, Mombaerts P, Tonegawa S, Yamamoto H, Itohara S: Homeostatic regulation of intestinal epithelia by intra epithelial γ/δ T cells. Proc Natl Acad Sci USA. 1995, 92: 6147-6151.PubMedCentralCrossRefPubMed Komano H, Fujiura Y, Kawaguchi M, Matsumoto S, Hashimoto Y, Obana S, Mombaerts P, Tonegawa S, Yamamoto H, Itohara S: Homeostatic regulation of intestinal epithelia by intra epithelial γ/δ T cells. Proc Natl Acad Sci USA. 1995, 92: 6147-6151.PubMedCentralCrossRefPubMed
11.
go back to reference Chien Y-H, Jores R, Crowley MP: Recognition by γ/δ T cells. Annu Rev Immunol. 1996, 14: 511-532. 10.1146/annurev.immunol.14.1.511.CrossRefPubMed Chien Y-H, Jores R, Crowley MP: Recognition by γ/δ T cells. Annu Rev Immunol. 1996, 14: 511-532. 10.1146/annurev.immunol.14.1.511.CrossRefPubMed
12.
go back to reference Tanaka Y, Morita CT, Tanaka Y, Nieves E, Brenner MB, Bloom BR: Natural and synthetic non peptide antigens recognized by human γ/δ T cells. Nature. 1995, 375: 155-158. 10.1038/375155a0.CrossRefPubMed Tanaka Y, Morita CT, Tanaka Y, Nieves E, Brenner MB, Bloom BR: Natural and synthetic non peptide antigens recognized by human γ/δ T cells. Nature. 1995, 375: 155-158. 10.1038/375155a0.CrossRefPubMed
13.
go back to reference Dieli F, Asherson GL, Romano GC, Sireci G, Gervasi F, Salerno A: IL-4 is essential for systemic transfer of delayed hypersensitivity by T cell lines. J Immunol. 1994, 152: 2698-2704.PubMed Dieli F, Asherson GL, Romano GC, Sireci G, Gervasi F, Salerno A: IL-4 is essential for systemic transfer of delayed hypersensitivity by T cell lines. J Immunol. 1994, 152: 2698-2704.PubMed
14.
go back to reference Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H: Differential production of interferon α and inter-leukin 4 in response to Th1 and Th2-stimulating pathogens by γδ T cells in vivo. Nature. 1995, 373: 255-257. 10.1038/373255a0.CrossRefPubMed Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H: Differential production of interferon α and inter-leukin 4 in response to Th1 and Th2-stimulating pathogens by γδ T cells in vivo. Nature. 1995, 373: 255-257. 10.1038/373255a0.CrossRefPubMed
15.
go back to reference Inaba G, Sakane T: Role of γδ T lymphocytes in the development of Behçet's disease. Clin Exp Immunol. 1997, 107: 241-247. 10.1111/j.1365-2249.1997.274-ce1159.x.PubMedCentralCrossRefPubMed Inaba G, Sakane T: Role of γδ T lymphocytes in the development of Behçet's disease. Clin Exp Immunol. 1997, 107: 241-247. 10.1111/j.1365-2249.1997.274-ce1159.x.PubMedCentralCrossRefPubMed
16.
go back to reference Hamzaoui K, Hamzaoui A, Hentati F, Kahan A, Ayed K, Chabbou A, Ben Hamida M, Hamza M: Phenotype and functional profile of T cell expressing gamma delta receptor from patients with active Behçet's disease. J Rheumatol. 1994, 21: 2301-2306.PubMed Hamzaoui K, Hamzaoui A, Hentati F, Kahan A, Ayed K, Chabbou A, Ben Hamida M, Hamza M: Phenotype and functional profile of T cell expressing gamma delta receptor from patients with active Behçet's disease. J Rheumatol. 1994, 21: 2301-2306.PubMed
17.
go back to reference Hasan A, Fortune F, Wilson A, Warr K, Shinnick T, Mizushima Y, van der Zee R, Stanford MR, Sanderson J, Lehner T: Role of gamma delta T cells in pathogenesis and diagnosis of Behçet's disease. Lancet. 1996, 347: 789-794. 10.1016/S0140-6736(96)90868-5.CrossRefPubMed Hasan A, Fortune F, Wilson A, Warr K, Shinnick T, Mizushima Y, van der Zee R, Stanford MR, Sanderson J, Lehner T: Role of gamma delta T cells in pathogenesis and diagnosis of Behçet's disease. Lancet. 1996, 347: 789-794. 10.1016/S0140-6736(96)90868-5.CrossRefPubMed
18.
go back to reference Salerno A, Dieli F: Role of gamma-delta T lymphocyte in immune response in humans and mice. Crit Rev Immunol. 1998, 18: 327-357.CrossRefPubMed Salerno A, Dieli F: Role of gamma-delta T lymphocyte in immune response in humans and mice. Crit Rev Immunol. 1998, 18: 327-357.CrossRefPubMed
19.
go back to reference Burk MR, Mori L, De Libero G: Human Vγ9-Vδ2 cells are stimulated in a cros-reactive fashion by a variety of phosphorylated metabolites. Eur J Immunol. 1995, 25: 2052-2058.CrossRefPubMed Burk MR, Mori L, De Libero G: Human Vγ9-Vδ2 cells are stimulated in a cros-reactive fashion by a variety of phosphorylated metabolites. Eur J Immunol. 1995, 25: 2052-2058.CrossRefPubMed
20.
go back to reference Bukowski JF, Morita CT, Tanaka Y, Bloom BR, Brenner MB, Band H: Vγ9-Vδ2 TCR-dependent recognition of non-peptide antigens and Daudi cells analysed by TCR gene transfer. J Immunol. 1995, 154: 998-1006.PubMed Bukowski JF, Morita CT, Tanaka Y, Bloom BR, Brenner MB, Band H: Vγ9-Vδ2 TCR-dependent recognition of non-peptide antigens and Daudi cells analysed by TCR gene transfer. J Immunol. 1995, 154: 998-1006.PubMed
21.
go back to reference Bukowski JF, Morita CT, Brenner MB: Recognition and destruction of virus-infected cells by human γ/δ CTL. J Immunol. 1994, 153: 5133-5140.PubMed Bukowski JF, Morita CT, Brenner MB: Recognition and destruction of virus-infected cells by human γ/δ CTL. J Immunol. 1994, 153: 5133-5140.PubMed
22.
go back to reference Ueta C, Kawasumi H, Fujiwara H: Interleukin-12 activates human γ/δ T cells: synergistic effect of tumor necrosis factor-α. Eur J Immunol. 1996, 26: 3066-3073.CrossRefPubMed Ueta C, Kawasumi H, Fujiwara H: Interleukin-12 activates human γ/δ T cells: synergistic effect of tumor necrosis factor-α. Eur J Immunol. 1996, 26: 3066-3073.CrossRefPubMed
23.
go back to reference Frassanito MA, Dammacco R, Cafforio P, Dammacco F: Th1 polarization of the immune response in Behçet's disease. Arthritis Rheum. 1999, 42: 1967-1974. 10.1002/1529-0131(199909)42:9<1967::AID-ANR24>3.0.CO;2-Z.CrossRefPubMed Frassanito MA, Dammacco R, Cafforio P, Dammacco F: Th1 polarization of the immune response in Behçet's disease. Arthritis Rheum. 1999, 42: 1967-1974. 10.1002/1529-0131(199909)42:9<1967::AID-ANR24>3.0.CO;2-Z.CrossRefPubMed
24.
go back to reference International Study Group for Behçet's Disease: Criteria for diagnosis of Behçet's disease. Lancet. 1990, 103: 177-184. International Study Group for Behçet's Disease: Criteria for diagnosis of Behçet's disease. Lancet. 1990, 103: 177-184.
25.
go back to reference Behçet's Disease Research Committee of Japan: Criteria for activity of Behçet's disease. In Annual Report of Behçet's Disease: Research Committee of Japan. Edited by: Sakane T. 1994, Japan: Ministry of health and welfare of Japan Behçet's Disease Research Committee of Japan: Criteria for activity of Behçet's disease. In Annual Report of Behçet's Disease: Research Committee of Japan. Edited by: Sakane T. 1994, Japan: Ministry of health and welfare of Japan
26.
go back to reference Dieli F, Sireci G, Di Sano C, Romano A, Titone L, Di Carlo P, Ivanyi J, Fournie JJ, Salerno A: Ligand-specific αβ and γδ T cell responses in childhood tuberculosis. J Infect Dis. 2000, 181: 294-301. 10.1086/315180.CrossRefPubMed Dieli F, Sireci G, Di Sano C, Romano A, Titone L, Di Carlo P, Ivanyi J, Fournie JJ, Salerno A: Ligand-specific αβ and γδ T cell responses in childhood tuberculosis. J Infect Dis. 2000, 181: 294-301. 10.1086/315180.CrossRefPubMed
27.
go back to reference Direskeneli H, Eksioglu-Demiralp E, Kibaroglu A, Yavuz S, Ergun T, Akoglu T: Oligoclonal T cell expansions in patients with Behçet's disease. Clin Exp Immunol. 1999, 117: 166-170. 10.1046/j.1365-2249.1999.00931.x.PubMedCentralCrossRefPubMed Direskeneli H, Eksioglu-Demiralp E, Kibaroglu A, Yavuz S, Ergun T, Akoglu T: Oligoclonal T cell expansions in patients with Behçet's disease. Clin Exp Immunol. 1999, 117: 166-170. 10.1046/j.1365-2249.1999.00931.x.PubMedCentralCrossRefPubMed
28.
go back to reference Janeway CA, Jones B, Hayday A: Specificity and function of T cells bearing γδ receptors. Immunol Today. 1988, 9: 73-76. 10.1016/0167-5699(88)91267-4.CrossRefPubMed Janeway CA, Jones B, Hayday A: Specificity and function of T cells bearing γδ receptors. Immunol Today. 1988, 9: 73-76. 10.1016/0167-5699(88)91267-4.CrossRefPubMed
29.
go back to reference Keystone E, Rittershaus C, Wood N, Snow K, Flatow J, Purvis J: Elevation of a γδ T cell subset in peripheral blood and synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 1991, 84: 78-82.PubMedCentralPubMed Keystone E, Rittershaus C, Wood N, Snow K, Flatow J, Purvis J: Elevation of a γδ T cell subset in peripheral blood and synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 1991, 84: 78-82.PubMedCentralPubMed
30.
go back to reference Roura-Mir IC, Alcalde L, Vargas F, Tolosa E, Obiols G, Foz M, Jaraquemada D, Pujol-Borrell R: γδ T lymphocytes in endocrine autoimmunity: evidence for expansion in Graves disease but not in type 1 diabetes. Clin Exp Immunol. 1993, 92: 288-295.PubMedCentralCrossRefPubMed Roura-Mir IC, Alcalde L, Vargas F, Tolosa E, Obiols G, Foz M, Jaraquemada D, Pujol-Borrell R: γδ T lymphocytes in endocrine autoimmunity: evidence for expansion in Graves disease but not in type 1 diabetes. Clin Exp Immunol. 1993, 92: 288-295.PubMedCentralCrossRefPubMed
31.
go back to reference Martins EBG, Graham AK, Chapman RW, Fleming KA: Elevation in γδ T lymphocytes in peripheral blood and livers of patients with primary sclerosing cholangitis and other autoimmune liver diseases. Hepatology. 1996, 23: 988-993.PubMed Martins EBG, Graham AK, Chapman RW, Fleming KA: Elevation in γδ T lymphocytes in peripheral blood and livers of patients with primary sclerosing cholangitis and other autoimmune liver diseases. Hepatology. 1996, 23: 988-993.PubMed
32.
go back to reference Shimonkevitz R, Colburn C, Burham JA, Murray RS, Kotzin BL: Clonal expansion of activated γδ T cells in recent-onset multiple sclerosis. Proc Natl Acad Sci USA. 1993, 90: 923-927.PubMedCentralCrossRefPubMed Shimonkevitz R, Colburn C, Burham JA, Murray RS, Kotzin BL: Clonal expansion of activated γδ T cells in recent-onset multiple sclerosis. Proc Natl Acad Sci USA. 1993, 90: 923-927.PubMedCentralCrossRefPubMed
33.
go back to reference Freysdottir J, Lau S, Fortune F: γδ T cells in Behçet's disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol. 1999, 118: 451-457. 10.1046/j.1365-2249.1999.01069.x.PubMedCentralCrossRefPubMed Freysdottir J, Lau S, Fortune F: γδ T cells in Behçet's disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol. 1999, 118: 451-457. 10.1046/j.1365-2249.1999.01069.x.PubMedCentralCrossRefPubMed
34.
go back to reference Sayinalp N, Ozcebe OI, Ozdemir O, Haznedaroglu IC, Dundar S, Kirazli S: Cytokines in Behçet's disease. J Rheumatol. 1996, 23: 321-322.PubMed Sayinalp N, Ozcebe OI, Ozdemir O, Haznedaroglu IC, Dundar S, Kirazli S: Cytokines in Behçet's disease. J Rheumatol. 1996, 23: 321-322.PubMed
35.
go back to reference Mege JL, Dilsen N, Sanguedolce V, Gul A, Bongrand P, Roux H, Ocal L, Inanc M, Capo C: Overproduction of monocyte derived tumor necrosis factor α, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet's disease: a comparative study with familial Mediterranean fever and healthy subjects. J Rheumatol. 1993, 20: 1544-1549.PubMed Mege JL, Dilsen N, Sanguedolce V, Gul A, Bongrand P, Roux H, Ocal L, Inanc M, Capo C: Overproduction of monocyte derived tumor necrosis factor α, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet's disease: a comparative study with familial Mediterranean fever and healthy subjects. J Rheumatol. 1993, 20: 1544-1549.PubMed
36.
go back to reference Kosar A, Haznedaroglu S, Karaaslan Y, Buyukasik Y, Haznedaroglu IC, Ozath D, Sayinalp N, Ozcebe O, Kirazli S, Dundar S: Effects of interferon-alpha2a treatment on serum levels of tumor necrosis factor-alpha, tumor necrosis alpha 2 receptor, interleukin-2, interleukin-2 receptor, and e-selectin in Behçet's disease. Rheumatol Intern. 1999, 19: 11-14. 10.1007/s002960050091.CrossRef Kosar A, Haznedaroglu S, Karaaslan Y, Buyukasik Y, Haznedaroglu IC, Ozath D, Sayinalp N, Ozcebe O, Kirazli S, Dundar S: Effects of interferon-alpha2a treatment on serum levels of tumor necrosis factor-alpha, tumor necrosis alpha 2 receptor, interleukin-2, interleukin-2 receptor, and e-selectin in Behçet's disease. Rheumatol Intern. 1999, 19: 11-14. 10.1007/s002960050091.CrossRef
37.
go back to reference Tartaglia LA, Pennica D, Goeddel DV: Ligand passing: the 75-kDA tumor necrosis factor (TNF) receptor recruits TNF for signalling by the 55-kDA TNF receptor. J Biol Chem. 1993, 268: 18542-18548.PubMed Tartaglia LA, Pennica D, Goeddel DV: Ligand passing: the 75-kDA tumor necrosis factor (TNF) receptor recruits TNF for signalling by the 55-kDA TNF receptor. J Biol Chem. 1993, 268: 18542-18548.PubMed
Metadata
Title
Vγ9/Vδ2 T lymphocytes in Italian patients with Behçet's disease - evidence for expansion, and tumour necrosis factor receptor II and interleukin-12 receptor β1 expression in active disease
Authors
Giovanni Triolo
Antonina Accardo-Palumbo
Francesco Dieli
Francesco Ciccia
Angelo Ferrante
Ennio Giardina
Caterina Di Sano
Giuseppe Licata
Publication date
01-10-2003
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2003
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar785

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