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Review Article

Adaptive immunity in the joint of rheumatoid arthritis

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Pages 1-11 | Received 18 Mar 2021, Accepted 06 May 2021, Published online: 30 May 2021

References

  • Humby F, Lewis M, Ramamoorthi N, et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann Rheum Dis. 2019;78(6):761–772.
  • Nerviani A, Di CM, Mahto A, et al. A pauci-immune synovial pathotype predicts inadequate response to TNFα-blockade in rheumatoid arthritis patients. Front Immunol. 2020;11:845.
  • Rivellese F, Humby F, Bugatti S, et al.; The PEAC‐R4RA Investigators. B cell synovitis and clinical phenotypes in rheumatoid arthritis: relationship to disease stages and drug exposure. Arthritis Rheumatol. 2020;72(5):714–725.
  • Orr C, Najm A, Biniecka M, et al. Synovial immunophenotype and anti-citrullinated peptide antibodies in rheumatoid arthritis patients: relationship to treatment response and radiologic prognosis. Arthritis Rheumatol. 2017;69(11):2114–2123.
  • Cantaert T, Brouard S, Thurlings RM, et al. Alterations of the synovial T cell repertoire in anti-citrullinated protein antibody-positive rheumatoid arthritis. Arthritis Rheum. 2009;60(7):1944–1956.
  • Bugatti S, Manzo A, Vitolo B, et al. High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a marker of severe disease. Rheumatology. 2014;53(10):1886–1895.
  • Takemura S, Braun A, Crowson C, et al. Lymphoid neogenesis in rheumatoid synovitis. J Immunol. 2001;167(2):1072–1080.
  • Klaasen R, Thurlings RM, Wijbrandts CA, et al. The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: a prospective study. Arthritis Rheum. 2009;60(11):3217–3224.
  • Manzo A, Paoletti S, Carulli M, et al. Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur J Immunol. 2005;35(5):1347–1359.
  • Shi K, Hayashida K, Kaneko M, et al. Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients. J Immunol. 2001;166(1):650–655.
  • Timmer TCG, Baltus B, Vondenhoff M, et al. Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis. Arthritis Rheum. 2007;56(8):2492–2502.
  • Cañete JD, Celis R, Yeremenko N, et al. Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis. Arthritis Res Ther. 2015;17(1):173.
  • Thurlings RM, Wijbrandts CA, Mebius RE, et al. Synovial lymphoid neogenesis does not define a specific clinical rheumatoid arthritis phenotype. Arthritis Rheum. 2008;58(6):1582–1589.
  • Cantaert T, Kolln J, Timmer T, et al. B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis. J Immunol. 2008;181(1):785–794.
  • Cañete JD, Santiago B, Cantaert T, et al. Ectopic lymphoid neogenesis in psoriatic arthritis. Ann Rheum Dis. 2007;66(6):720–726.
  • van de Sande MGH, Thurlings RM, Boumans MJH, et al. Presence of lymphocyte aggregates in the synovium of patients with early arthritis in relationship to diagnosis and outcome: is it a constant feature over time? Ann Rheum Dis. 2011;70(4):700–703.
  • Cañete JD, Celis R, Moll C, et al. Clinical significance of synovial lymphoid neogenesis and its reversal after anti-tumour necrosis factor alpha therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68(5):751–756.
  • Mellors RC, Heimer R, Corcos J, et al. Cellular origin of rheumatoid factor. J Exp Med. 1959;110(6):875–886.
  • Reparon-Schuijt CC, van Esch WJ, van Kooten C, et al. Functional analysis of rheumatoid factor-producing B cells from the synovial fluid of rheumatoid arthritis patients. Arthritis Rheum. 1998;41(12):2211–2220.
  • Otten HG, Daha MR, Dolhain RJ, et al. Rheumatoid factor production by mononuclear cells derived from different sites of patients with rheumatoid arthritis. Clin Exp Immunol. 1993;94(2):236–240.
  • Caspi D, Anouk M, Golan I, et al. Synovial fluid levels of anti-cyclic citrullinated peptide antibodies and IgA rheumatoid factor in rheumatoid arthritis, psoriatic arthritis, and osteoarthritis. Arthritis Rheum. 2006;55(1):53–56.
  • van de Sande MGH, de Hair MJH, van der Leij C, et al. Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase. Ann Rheum Dis. 2011;70(5):772–777.
  • Reparon-Schuijt CC, van Esch WJE, van Kooten C, et al. Secretion of anti–citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis. Arthritis Rheum. 2001;44(1):41–47.
  • Kerkman PF, Kempers AC, van der Voort EIH, et al. Synovial fluid mononuclear cells provide an environment for long-term survival of antibody-secreting cells and promote the spontaneous production of anti-citrullinated protein antibodies. Ann Rheum Dis. 2016;75(12):2201–2207.
  • Snir O, Widhe M, Hermansson M, et al. Antibodies to several citrullinated antigens are enriched in the joints of rheumatoid arthritis patients. Arthritis Rheum. 2010;62(1):44–52.
  • Sohrabian A, Mathsson-Alm L, Hansson M, et al. Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis. Ann Rheum Dis. 2018;77(9):1345–1353.
  • Doorenspleet ME, Klarenbeek PL, de Hair MJH, et al. Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity. Ann Rheum Dis. 2014;73(4):756–762.
  • Elliott SE, Kongpachith S, Lingampalli N, et al. B cells in rheumatoid arthritis synovial tissues encode focused antibody repertoires that include antibodies that stimulate macrophage TNF-α production. Clin Immunol. 2020;212:108360.
  • Steen J, Forsström B, Sahlström P, et al. Recognition of amino acid motifs, rather than specific proteins, by human plasma cell-derived monoclonal antibodies to posttranslationally modified proteins in rheumatoid arthritis. Arthritis Rheumatol. 2019;71(2):196–209.
  • Germar K, Fehres CM, Scherer HU, et al. Generation and characterization of anti-citrullinated protein antibody-producing B cell clones from rheumatoid arthritis patients. Arthritis Rheumatol. 2019;71(3):340–350.
  • Kim HJ, Krenn V, Steinhauser G, et al. Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis. J Immunol. 1999;162(5):3053–3062.
  • Humby F, Bombardieri M, Manzo A, et al. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med. 2009;6(1):e1.
  • Corsiero E, Bombardieri M, Carlotti E, et al. Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs. Ann Rheum Dis. 2016;75(10):1866–1875.
  • Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med. 2013;5(178): 178ra40.
  • Corsiero E, Carlotti E, Jagemann L, et al. H and L chain affinity maturation and/or Fab N-glycosylation influence immunoreactivity toward neutrophil extracellular trap antigens in rheumatoid arthritis synovial B cell clones. J Immunol. 2020;204(9):2374–2379.
  • Croia C, Serafini B, Bombardieri M, et al. Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Ann Rheum Dis. 2013;72(9):1559–1568.
  • Chatzidionysiou K, Lie E, Nasonov E, et al. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries. Ann Rheum Dis. 2011;70(9):1575–1580.
  • Toubi E, Kessel A, Slobodin G, et al. Changes in macrophage function after rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66(6):818–820.
  • Thurlings RM, Vos K, Wijbrandts CA, et al. Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response. Ann Rheum Dis. 2008;67(7):917–925.
  • Yeo L, Toellner K-M, Salmon M, et al. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis. 2011;70(11):2022–2028.
  • Zhang F, Wei K, Slowikowski K, Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019;20(7):928–942.
  • Cowan GJM, Miles K, Capitani L, et al. Human autoimmunity, a substantial component of the B cell repertoire consists of polyclonal, barely mutated IgG + ve B cells. Front Immunol. 2020;11:395.
  • Floudas A, Neto N, Marzaioli V, et al. Pathogenic, glycolytic PD-1+ B cells accumulate in the hypoxic RA joint. JCI Insight. 2020;5(21):e139032.
  • Störch H, Zimmermann B, Resch B, et al. Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return. Ann Rheum Dis. 2016;75(5):924–932.
  • Kristyanto H, Blomberg NJ, Slot LM, et al. Persistently activated, proliferative memory autoreactive B cells promote inflammation in rheumatoid arthritis. Sci Transl Med. 2020;12(570):eaaz5327.
  • Yeo L, Lom H, Juarez M, et al. Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis. Ann Rheum Dis. 2015;74(5):928–935.
  • Amara K, Clay E, Yeo L, et al. B cells expressing the IgA receptor FcRL4 participate in the autoimmune response in patients with rheumatoid arthritis. J Autoimmun. 2017;81:34–43.
  • Meednu N, Zhang H, Owen T, et al. Production of RANKL by memory B cells: a link between B cells and bone erosion in rheumatoid arthritis. Arthritis Rheumatol. 2016;68(4):805–816.
  • Ota Y, Niiro H, Ota S-I, et al. Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis. Arthritis Res Ther. 2016;18:67.
  • Nakayama T, Yoshimura M, Higashioka K, et al. Type 1 helper T cells generate CXCL9/10-producing T-bet + effector B cells potentially involved in the pathogenesis of rheumatoid arthritis. Cell Immunol. 2021;360:104263.
  • Takemura S, Klimiuk PA, Braun A, et al. T cell activation in rheumatoid synovium is B cell dependent. J Immunol. 2001;167(8):4710–4718.
  • Kaibara N, Yamada H, Shuto T, et al. Comparative histopathological analysis between tenosynovitis and joint synovitis in rheumatoid arthritis. Histopathology. 2008;52(7):856–864.
  • Yamada H, Nakashima Y, Okazaki K, et al. Preferential accumulation of activated Th1 cells not only in rheumatoid arthritis but also in osteoarthritis joints. J Rheumatol. 2011;38(8):1569–1575.
  • Klareskog L, Stolt P, Lundberg K, et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006;54(1):38–46.
  • Kondo Y, Yokosawa M, Kaneko S, et al. Review: transcriptional regulation of CD4+ T cell differentiation in experimentally induced arthritis and rheumatoid arthritis. Arthritis Rheumatol. 2018;70(5):653–661.
  • Sokolove J, Schiff M, Fleischmann R, et al. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis. 2016;75(4):709–714.
  • Oryoji K, Yoshida K, Kashiwado Y, et al. Shared epitope positivity is related to efficacy of abatacept in rheumatoid arthritis. Ann Rheum Dis. 2018;77(8):1234–1236.
  • Firestein GS, Alvaro-Gracia JM, Maki R, et al. Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol. 1990;144(9):3347–3353.
  • Chen E, Keystone EC, Fish EN. Restricted cytokine expression in rheumatoid arthritis. Arthritis Rheum. 1993;36(7):901–910.
  • Firestein GS, Zvaifler NJ. How important are T cells in chronic rheumatoid synovitis? Arthritis Rheum. 1990;33(6):768–773.
  • Rouvier E, Luciani MF, Mattei MG, et al. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993;150(12):5445–5456.
  • Chabaud M, Durand JM, Buchs N, et al. A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 1999;42(5):963–970.
  • Kotake S, Udagawa N, Takahashi N, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103(9):1345–1352.
  • Yamada H. Current perspectives on the role of IL-17 in autoimmune disease. J Inflamm Res. 2010;3:33–44.
  • Nakae S, Nambu A, Sudo K, et al. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171(11):6173–6177.
  • Lubberts E, Koenders MI, Oppers-Walgreen B, et al. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. 2004;50(2):650–659.
  • Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123–1132.
  • Annunziato F, Cosmi L, Santarlasci V, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204(8):1849–1861.
  • Yamada H, Nakashima Y, Okazaki K, et al. Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67(9):1299–1304.
  • Ito Y, Usui T, Kobayashi S, et al. Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. Arthritis Rheum. 2009;60(8):2294–2303.
  • Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: what can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175–187.
  • Burmester GR, McInnes IB, Kremer JM, et al. Mavrilimumab, a fully human granulocyte-macrophage colony-stimulating factor receptor α monoclonal antibody: long-term safety and efficacy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2018;70(5):679–689.
  • Reynolds G, Gibbon JR, Pratt AG, et al. Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis. Ann Rheum Dis. 2016;75(5):899–907.
  • Noster R, Riedel R, Mashreghi M-F, et al. IL-17 and GM-CSF expression are antagonistically regulated by human T helper cells. Sci Transl Med. 2014;6(241):241ra80.
  • Yamada H, Haraguchi A, Sakuraba K, et al. Th1 is the predominant helper T cell subset that produces GM-CSF in the joint of rheumatoid arthritis. RMD Open. 2017;3(1):e000487.
  • Fonseka CY, Rao DA, Teslovich NC, et al. Mixed-effects association of single cells identifies an expanded effector CD4+ T cell subset in rheumatoid arthritis. Sci Transl Med. 2018;10(463):eaaq0305.
  • Hashimoto M, Kamphorst AO, Im SJ, et al. CD8 T cell exhaustion in chronic infection and cancer: opportunities for interventions. Annu Rev Med. 2018;69:301–318.
  • Hatachi S, Iwai Y, Kawano S, et al. CD4+ PD-1+ T cells accumulate as unique anergic cells in rheumatoid arthritis synovial fluid. J Rheumatol. 2003;30(7):1410–1419.
  • Rao DA, Gurish MF, Marshall JL, et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature. 2017;542(7639):110–114.
  • Takeshita M, Suzuki K, Kondo Y, et al. Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell. Ann Rheum Dis. 2019;78(10):1346–1356.
  • Fortea-Gordo P, Nuño L, Villalba A, et al. Two populations of circulating PD-1hiCD4 T cells with distinct B cell helping capacity are elevated in early rheumatoid arthritis. Rheumatology (Oxford). 2019;58(9):1662–1673.
  • Lebre MC, Vieira PL, Tang MW, et al. Synovial IL-21/TNF-producing CD4+ T cells induce joint destruction in rheumatoid arthritis by inducing matrix metalloproteinase production by fibroblast-like synoviocytes. J Leukoc Biol. 2017;101(3):775–783.
  • Sakuragi T, Yamada H, Haraguchi A, et al. Autoreactivity of peripheral helper T cells in the joints of rheumatoid arthritis. JI. 2021;206(9):2045–2051.
  • Manzo A, Vitolo B, Humby F, et al. Mature antigen-experienced T helper cells synthesize and secrete the B cell chemoattractant CXCL13 in the inflammatory environment of the rheumatoid joint. Arthritis Rheum. 2008;58(11):3377–3387.
  • Kobayashi S, Murata K, Shibuya H, et al. A distinct human CD4+ T cell subset that secretes CXCL13 in rheumatoid synovium: CXCL13-producing CD4+ T cells in RA synovium. Arthritis Rheum. 2013;65(12):3063–3072.
  • Yoshitomi H, Kobayashi S, Miyagawa-Hayashino A, et al. Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments. Nat Commun. 2018;9(1):3762.
  • Kobayashi S, Watanabe T, Suzuki R, et al. TGF-β induces the differentiation of human CXCL13-producing CD4(+) T cells. Eur J Immunol. 2016;46(2):360–371.
  • Eri T, Kawahata T, Kanzaki T, et al. Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1 + CXCR5-/dim B-helper T cell induction. Sci Rep. 2017;7:46037.
  • Carvalheiro H, Duarte C, Silva-Cardoso S, et al. CD8+ T cell profiles in patients with rheumatoid arthritis and their relationship to disease activity. Arthritis Rheumatol. 2015;67(2):363–371.
  • Higashioka K, Yoshimura M, Sakuragi T, et al. Human PD-1hiCD8+ T cells are a cellular source of IL-21 in rheumatoid arthritis. Front Immunol. 2021;12:654623.
  • Wagner UG, Kurtin PJ, Wahner A, et al. The role of CD8+ CD40L + T cells in the formation of germinal centers in rheumatoid synovitis. J Immunol. 1998;161(11):6390–6397.
  • Kang YM, Zhang X, Wagner UG, et al. CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J Exp Med. 2002;195(10):1325–1336.
  • Keystone EC, Minden M, Klock R, et al. Structure of T cell antigen receptor beta chain in synovial fluid cells from patients with rheumatoid arthritis. Arthritis Rheum. 1988;31(12):1555–1557.
  • Jenkins RN, Nikaein A, Zimmermann A, et al. T cell receptor V beta gene bias in rheumatoid arthritis. J Clin Invest. 1993;92(6):2688–2701.
  • Alam A, Lulé J, Coppin H, et al. T-cell receptor variable region of the beta-chain gene use in peripheral blood and multiple synovial membranes during rheumatoid arthritis. Hum Immunol. 1995;42(4):331–339.
  • Ikeda Y, Masuko K, Nakai Y, et al. High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthritis patients suggest the occurrence of common antigen-driven immune responses. Arthritis Rheum. 1996;39(3):446–453.
  • Alam A, Lambert N, Lulé J, et al. Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis. J Immunol. 1996;156(9):3480–3485.
  • Klarenbeek PL, de Hair MJH, Doorenspleet ME, et al. Inflamed target tissue provides a specific niche for highly expanded T-cell clones in early human autoimmune disease. Ann Rheum Dis. 2012;71(6):1088–1093.
  • Musters A, Klarenbeek PL, Doorenspleet ME, et al. In rheumatoid arthritis, synovitis at different inflammatory sites is dominated by shared but patient-specific T cell clones. J Immunol. 2018;201(2):417–422.
  • Song J, Schwenzer A, Wong A, et al. Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis. JCI Insight. 2021;6(5):145217.
  • Pieper J, Dubnovitsky A, Gerstner C, et al. Memory T cells specific to citrullinated α-enolase are enriched in the rheumatic joint. J Autoimmun. 2018;92:47–56.
  • Chemin K, Pollastro S, James E, et al. A novel HLA-DRB1*10:01-restricted T cell epitope from citrullinated type II collagen relevant to rheumatoid arthritis. Arthritis Rheumatol. 2016;68(5):1124–1135.
  • Rims C, Uchtenhagen H, Kaplan MJ, et al. Citrullinated aggrecan epitopes as targets of autoreactive CD4+ T cells in patients with rheumatoid arthritis. Arthritis Rheumatol. 2019;71(4):518–528.
  • James EA, Rieck M, Pieper J, et al. Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their frequency is influenced by disease duration and therapy. Arthritis Rheumatol. 2014;66(7):1712–1722.
  • Snir O, Rieck M, Gebe JA, et al. Identification and functional characterization of T cells reactive to citrullinated vimentin in HLA-DRB1*0401-positive humanized mice and rheumatoid arthritis patients. Arthritis Rheum. 2011;63(10):2873–2883.
  • Yoshitomi H. CXCL13-producing PD-1hiCXCR5- helper T cells in chronic inflammation. Immunol Med. 2020;43(4):156–160.
  • Christophersen A, Lund EG, Snir O, et al. Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions. Nat Med. 2019;25(5):734–737.
  • Brennan FM, Hayes AL, Ciesielski CJ, et al. Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells. Arthritis Rheum. 2002;46(1):31–41.
  • Brennan FM, Smith NMG, Owen S, et al. Resting CD4+ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell function. Arthritis Res Ther. 2008;10(2):R36.
  • Bryant J, Ahern DJ, Brennan FM. CXCR4 and vascular cell adhesion molecule 1 are key chemokine/adhesion receptors in the migration of cytokine-activated T cells. Arthritis Rheum. 2012;64(7):2137–2146.
  • Shadidi KR, Aarvak T, Jeansson S, et al. T-cell responses to viral, bacterial and protozoan antigens in rheumatoid inflammation. Selective migration of T cells to synovial tissue. Rheumatology (Oxford). 2001;40(10):1120–1125.
  • Tan LC, Mowat AG, Fazou C, et al. Specificity of T cells in synovial fluid: high frequencies of CD8+ T cells that are specific for certain viral epitopes. Arthritis Res. 2000;2(2):154.
  • Celis L, Vandevyver C, Geusens P, et al. Clonal expansion of mycobacterial heat-shock protein-reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients. Arthritis Rheum. 1997;40(3):510–519.
  • Fazou C, Yang H, Mc Michael AJ, et al. Epitope specificity of clonally expanded populations of CD8+ T cells found within the joints of patients with inflammatory arthritis. Arthritis Rheum. 2001;44(9):2038–2045.