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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 2/2000

Open Access 01-02-2000 | Research article

Specificity of T cells in synovial fluid: high frequencies of CD8+ T cells that are specific for certain viral epitopes

Authors: Linda C Tan, Alastair G Mowat, Chrysoula Fazou, Tim Rostron, Helen Roskell, P Rod Dunbar, Claire Tournay, François Romagné, Marie-Alix Peyrat, Elisabeth Houssaint, Marc Bonneville, Alan B Rickinson, Andrew J McMichael, Margaret FC Callan

Published in: Arthritis Research & Therapy | Issue 2/2000

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Statement of findings

CD8+ T cells dominate the lymphocyte population insynovial fluid in chronic inflammatory arthritis. It is known that theseCD8+ T cells are often clonally or oligoclonally expanded, but theirspecificity and their relevance to the pathogenesis of joint disease hasremained unclear. We found that as many as 15.5% of synovial CD8+ Tcells may be specific for a single epitope from an Epstein-Barr virus lyticcycle protein. The virus-specific T cells within the joint showed increasedexpression of markers of activation and differentiation compared with those inthe periphery, and retained their functional capacity to secreteproinflammatory cytokines on stimulation. These activated, virus-specificCD8+ T cells could therefore interact with synoviocytes, either bycell-cell contact or by a cytokine network, and play a 'bystander'role in the maintenance of inflammation in patients with arthritis.
Literature
1.
Rickinson AB, Kieff E: Epstein-Barr virus. In: Virology, 3rd ed. Edited by Fields BN, Knipe DM, Howley PM.Philadelphia: Lippincott-Raven,. 1996, 2397-2446.
2.
Massuci MG, Ernberg I: Epstein-Barr virus: adaptation to a life within the immunesystem. Trends Microbiol. 1994, 2: 125-130.CrossRef
3.
Sixbey JW, Nedrud JG, Raab-Traub N, Hanes RA, Pagano JS: Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med. 1984, 310: 1225-1230.PubMedCrossRef
4.
Tierney RJ, Steven N, Young LS, Rickinson AB: Epstein-Barr virus latency in blood mononuclear cells: analysis ofviral gene transcription during primary infection and in the carrier state. J Virol. 1994, 68: 7374-7385.PubMedPubMedCentral
5.
Murray RJ, Kurilla MG, Brooks JM: Identification of target antigens for the human cytotoxic T cellresponse to Epstein-Barr virus (EBV): implications for the immune control ofEBV-positive malignancies. J Exp Med. 1992, 176: 157-168.PubMedCrossRef
6.
Khanna R, Burrows SR, Kurilla MG: Localisation of Epstein-Barr virus cytotoxic T cell epitopes usingrecombinant vaccinia: implications for vaccine development. J Exp Med. 1992, 176: 169-176.PubMedCrossRef
7.
Tan LC, Gudgeon N, Annels NE: T cells specific for EBV in healthy virus carriers. J Immunol. 1999, 162: 1827-1835.PubMed
8.
Bogedain C, Wolf H, Modrow S, Stuber G, Jilg W: Specific cytotoxic T lymphocytes recognise the immediate-earlytransactivator Zta of Epstein-Barr virus. J Virol. 1995, 69: 4872-4879.PubMedPubMedCentral
9.
Steven N, Annels NE, Kumar A: Immediate early and early lytic cycle proteins are frequent targetsof the Epstein-Barr virus-induced cytotoxic T cell response. J Exp Med. 1997, 185: 1605-1617.PubMedPubMedCentralCrossRef
10.
Callan MFC, Tan L, Annels N: Direct visualisation of antigen-specific CD8+ T cellsduring the primary immune response to Epstein Barr virus in vivo. J Exp Med. 1998, 187: 1395-1402.PubMedPubMedCentralCrossRef
11.
Catalano MA, Carson DA, Slovin SF, Richman DD, Vaughan JH: Antibodies to Epstein-Barr virus-determined antigens in normalsubjects and in patients with seropositive rheumatoid arthritis. Proc Natl Acad Sci USA. 1979, 76: 5825-5828.PubMedPubMedCentralCrossRef
12.
Yao QY, Rickinson AB, Gaston JS, Epstein MA: Disturbance of the Epstein-Barr virus-host balance in rheumatoidarthritis patients: a quantitative study. Clin Exp Immunol. 1986, 64: 302-310.PubMedPubMedCentral
13.
Baboonian C, Venables PJ, Williams DG, Williams RO, Maini RN: Cross reaction of antibodies to a glycine/alanine repeat sequence ofEpstein-Barr virus nuclear antigen-1 with collagen, cytokeratin, and actin. Ann Rheum Dis. 1991, 50: 772-775.PubMedPubMedCentralCrossRef
14.
Scotet E, David-Ameline J, Peyrat M-A: T cell response to Epstein-Barr virus transactivators in chronicrheumatoid arthritis. J Exp Med. 1996, 184: 1791-1800.PubMedCrossRef
15.
David-Ameline J, Lim A, Davodeau F: Selection of T cells reactive against autologous B lymphoblastoidcells during chronic rheumatoid arthritis. J Immunol. 1996, 157: 4697-4706.PubMed
16.
Scotet E, Peyrat M-A, Saulquin X: Frequent enrichment for CD8 T cells reactive against common herpesviruses in chronic inflammatory lesions: towards a reassessment of thephysiopathological significance of T cell clonal expansions found in autoimmuneinflammatory processes. Eur J Immunol. 1999, 29: 973-985. 10.1002/(SICI)1521-4141(199903)29:03<973::AID-IMMU973>3.0.CO;2-P.PubMedCrossRef
17.
Altman JD, Moss PAH, Goulder PR: Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996, 274: 94-96.PubMedCrossRef
18.
Wills MR, Carmichael AJ, Mynard K: The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirusis dominated by structural protein pp65: frequency, specificity, and T-cellreceptor usage of pp65-specific CTL. J Virol. 1996, 70: 7569-7579.PubMedPubMedCentral
19.
Morrison J, Elvin J, Latron F: Identification of the nonamer peptide from influenza A matrixprotein and the role of pockets of HLA A2 in its recognition by cytotoxic Tlymphocytes. Eur J Immunol. 1992, 22: 903-907.PubMedCrossRef
20.
Bunce M, O'Neil CM, Barnardo MC: Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3,DRB4, DRB5 and DQB1 by PCR with 144 primer mixes utilising sequence-specificprimers (PCR-SSP). Tissue Antigens. 1995, 46: 355-367.PubMedCrossRef
21.
Burrows SR, Rodda SJ, Suhrbier A, Geysen HM, Moss DJ: The specificity of recognition of a cytotoxic T lymphocyteepitope. Eur J Immunol. 1992, 22: 191-195.PubMedCrossRef
22.
Iannone F, Corrigall VM, Kingsley GH, Panayi GS: Evidence for the continuous recruitment and activation of T cellsinto the joints of patients with rheumatoid arthritis. Eur J Immunol. 1994, 24: 2706-2713.PubMedCrossRef
23.
Spertini O, Luscinskas FW, Kansas GS: Leukocyte adhesion molecule (LAM-1, L selectin) interacts with aninducible endothelial cell ligand to support leucocyte adhesion. J Immunol . 1991, 147: 2565-2573.PubMed
24.
Akbar AN, Terry L, Timms A, Beverley PC, Janossy G: Loss of CD45R and gain of UCHL1 reactivity is a feature of primed Tcells. J Immunol. 1988, 140: 2171-2178.PubMed
25.
D'Angeac AD, Monier S, Pilling D: CD57+ T lymphocytes are derived from CD57-precursors by differentiation occurring in late immune responses. Eur J Immunol . 1994, 24: 1503-1511.PubMedCrossRef
26.
Azuma M, Phillips JH, Lanier LL: CD28- T lymphocytes. Antigenic and functionalproperties. J Immunol. 1993, 150: 1147-1159.PubMed
27.
Qin S, Rottman JB, Myers P: The chemokine receptors CXCR3 and CCR5 mark subsets of T cellsassociated with certain inflammatory reactions. J Clin Invest . 1998, 101: 746-754.PubMedPubMedCentralCrossRef
28.
Bonecchi R, Bianchi G, Bordignon PP: Differential expression of chemokine receptors and chemotacticresponsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med . 1998, 187: 129-134.PubMedPubMedCentralCrossRef
29.
30.
Yokota A, Murata N, Saiki O: High avidity state of leukocyte function-associated antigen-1 onrheumatoid synovial fluid T lymphocytes. J Immunol. 1995, 155: 4118-4124.PubMed
31.
Dustin ML, Springer TA: Lymphocyte function-associated antigen-1 (LFA-1) interaction withintercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanismsfor lymphocyte adhesion to cultured endothelial cells. J Cell Biol. 1988, 107: 321-331.PubMedCrossRef
32.
Einsele H, Steidle M, Muller CA: Demonstration of cytomegalovirus (CMV) DNA and anti-CMV response inthe synovial membranes and serum of patients with rheumatoid arthritis. J Rheumatol. 1992, 19: 677-681.PubMed
33.
Brousset P, Caulier M, Cantagrel A: Absence of Epstein-Barr virus carrying cells in synovial membranesand subcutaneous nodules of patients with rheumatoid arthritis. Ann Rheum Dis. 1993, 52: 608-609.PubMedPubMedCentralCrossRef
34.
Zhang L, Nikkari S, Skurnik M: Detection of herpesviruses by polymerase chain reaction inlymphocytes from patients with rheumatoid arthritis. Arthritis Rheum. 1993, 36: 1080-1086.PubMedCrossRef
35.
Mousavi-Jazi M, Bostrom L, Lovmark C: Infrequent detection of cytomegalovirus and Epstein-Barr virus DNAin synovial membrance of patients with rheumatoid arthritis. J Rheumatol . 1998, 25: 623-628.PubMed
36.
Takei M, Mitamura K, Fujiwara S: Detection of Epstein-Barr virus-encoded small RNA 1 and latentmembrane protein 1 in synovial lining cells from rheumatoid arthritispatients. Int Immunol. 1997, 9: 739-743.PubMedCrossRef
37.
Koide J, Takada K, Sugiura M: Spontaneous establishment of an Epstein-Barr virus-infectedfibroblast line from the synovial tissue of a rheumatoid arthritis patient. J Virol. 1997, 71: 2478-2481.PubMedPubMedCentral
38.
Edinger JW, Bonneville M, Scotet E: EBV gene expression not altered in rheumatoid synovia despite thepresence of EBV antigen-specific T cell clones. J Immunol . 1999, 162: 3694-3701.PubMed
39.
Albert M, Sauter B, Bhardwaj N: Dendritic cells acquire antigen from apoptotic cells and induceclass I restricted CTLs. Nature. 1998, 392: 86-89.PubMedCrossRef
40.
Misko IS, Cross SM, Khanna R: Cross reactive recognition of viral, self and bacterial peptideligands by human class I-restricted cytotoxic T lymphocyte clonotypes:implications for molecular mimicry in autoimmune disease. Proc Natl Acad Sci USA. 1999, 96: 2279-2284.PubMedPubMedCentralCrossRef
41.
Pilling D, Akbar AN, Girdlestone J: Interferon-γ mediates stromal rescue of T cells from apoptosis. Eur J Immmunol. 1999, 29: 1041-1050.CrossRef
42.
Klimiuk PA, Yang H, Goronzy JJ, Weyand CM: Production of cytokines and metalloproteinases in rheumatoidsynovitis is T cell dependent. Clin Immunol. 1999, 90: 65-78. 10.1006/clim.1998.4618.PubMedCrossRef
43.
Sebbag M, Parry SL, Brennan FL, Feldmann M: Cytokine stimulation of T lymphocytes regulates their capacity toinduce monocyte production of tumor necrosis factor-alpha, but notinterleukin-10: possible relevance to pathophysiology of rheumatoidarthritis. Eur J Immunol. 1997, 27: 624-632.PubMedCrossRef
44.
Paliard X, West SG, Lafferty JA: Evidence for the effects of a superantigen in rheumatoidarthritis. Science . 1991, 253: 325-329.PubMedCrossRef
Metadata
Title
Specificity of T cells in synovial fluid: high frequencies of CD8+ T cells that are specific for certain viral epitopes
Authors
Linda C Tan
Alastair G Mowat
Chrysoula Fazou
Tim Rostron
Helen Roskell
P Rod Dunbar
Claire Tournay
François Romagné
Marie-Alix Peyrat
Elisabeth Houssaint
Marc Bonneville
Alan B Rickinson
Andrew J McMichael
Margaret FC Callan
Publication date
01-02-2000
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 2/2000
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar80

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