Abstract
The affected joints of patients with rheumatoid arthritis (RA) contain a large number of T cells, of which those expressing specific T cell receptor (TCR) Vβ chains are thought to play an important role in the pathogenesis of RA. The TCR Vβ repertoire of large lymphoblasts and small non-blasts from the synovial fluid (SF) and peripheral blood (PB) of RA patients, as well as their responsiveness to staphylococcal enterotoxin A (SEA), was investigated. TCR Vβ repertoire was examined with a semiquantitative reverse transcription-polymerase chain reaction assay, as was expression of genes encoding interleukin (IL)-2 and IL-4. Production of IL-2 and IL-4 was measured with a bioassay and an enzyme immunoassay system, respectively. Expression of TCR Vβ6.1-3, 7 and 15 was more frequent among large lymphoblasts than among small non-blasts in paired preparations from the 14 SF of 14 RA patients. TCR Vβ7 was expressed more frequently by large lymphoblasts than by small non-blasts in the PB of eight RA patients. The usage of TCR Vβ6.1-3 and 7 by large lymphoblasts in SF from RA patients significantly reduced in response to SEA stimulation. Both IL-2 production and gene expression as well as IL-4 production and gene expression in large lymphoblasts from the SF of RA patients increased to a lesser extent in response to SEA stimulation compared with the effects observed in paired small non-blasts. In summary, large lymphoblasts expressing TCR Vβ6.1-3, 7 and 15 were selectively expanded in SF of RA patients, and those bearing TCR Vβ6.1-3 or 7 were selectively unresponsive to SEA stimulation. These results indicate that SF lymphoblasts bearing Vβ6.1-3 or 7 were anergic with regard to stimulation with superantigen, suggesting the implication of a superantigen in previous activation of T cells in SF of RA patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Haqqi TM, Banerjee S, Jones WLet al., Identification of T cell receptor Vβ deletion mutant mouse strain AU/ssJ (H-2q) which is resistant to collagen-induced arthritis,Immunogenetics 29, 180–185 (1989).
Banerjee S, Andersson GD, Luthra HSet al., Influence of complement C5 and Vβ T cell receptor mutations on susceptibility to collagen-induced arthritis in mice,J Immunol 142, 2237–2243 (1989).
Haqqi TM, Anderson GD, Subhashis Bet al., Restricted heterogeneity in T-cell antigen receptor Vβ gene usage in the lymph nodes and arthritic joints of mice,Proc Natl Acad Sci USA 89, 1253–1255 (1992).
Sottini A, Imberti L, Gorla Ret al., Restricted expression of T cell receptor Vβ but not Vα genes in rheumatoid arthritis,Eur J Immunol 21, 461–466 (1991).
Paliard X, West SG, Lafferty JAet al., Evidence for the effect of a superantigen in rheumatoid arthritis,Science 253, 325–329 (1991).
Howell MD, Diveley JP, Lundeen KAet al., Limited T-cell receptor β chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis,Proc Natl Acad Sci USA 88, 10921–10925 (1991).
Williams WV, Fang Q, Demarco Det al., Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium,J Clin Invest 90, 326–333 (1992).
Zagon G, Tumang JR, Yixin Let al., Increased frequency o Vβ 17-positive T cells in patients with rheumatoid arthritis,Arthritis Rheum 37, 1431–1440 (1994).
Jenkins RN, Nikaein A, Zimmermann Aet al., T cell receptor Vβ gene bias in rheumatoid arthritis,J Clin Invest 92, 2688–2701 (1993).
Maruyama T, Saito I, Miyake Set al., A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis,Eur J Immunol 23, 2059–2065 (1993).
Callahan JE, Herman A, Kappler JWet al., Stimulation of B10.BR T cells with superantigenic staphylococcal toxins,J Immunol 144, 2473–2479 (1990).
Hudson KR, Robinson H, Fraser JD, Two adjacent residues in staphylococcal enterotoxins A and E determine T cell receptor Vβ specificity,J Exp Med 177, 175–184 (1993).
Takimoto H, Yoshikai Y, Kishihara Ket al., Stimulation of all T cells bearing Vβ1, Vβ3, Vβ11 and Vβ12 by staphylococcal enterotoxin A,Eur J Immunol 20, 617–621 (1990).
Arnett FC, Edworthy S, Bloch DAet al., The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis,Arthritis Rheum 31 315–324 (1988).
Uchiyama T, Saito S, Inoko Het al., Relative activities of distinct isotypes of murine and human major histocompatibility complex class II molecules in binding toxic shock syndrome toxin 1 and determination of CD antigens expressed on T cells generated upon stimulation by the toxin,Infect Immun 58 3877–3882 (1990).
Kato H, Fujimaki W, Marimatsu Het al., Study of TCR Vβ usage in superantigen-reactive human T cells by the RT-PCR method,J Tokyo Wom Med Coll 64, 985–993 (1994).
Chomczynski P, Sacchi N, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction,Anal Biochem 162, 156–159 (1987).
Choi Y, Kotzin B, Herron Let al., Interaction ofStaphylococcus aureus toxin ‘superantigens’ with human T cells,Proc Natl Acad Sci USA 86, 8941–8945 (1989).
Taniguchi T, Matsui H, Fujita Tet al., Structure and expression of a cloned cDNA for human interleukin-2,Nature 302, 305–310 (1983).
Yamamura M, Uemura K, Deans RJet al., Defining protective response to pathogens: cytokine profiles in leprosy lesions,Science 254, 277–279 (1991).
Güssow D, Rein R, Ginjarr Iet al., The human β2-microglobulin gene. Pimary structure and definition of the transcriptional unit,J Immunol 139, 3132–3138 (1987).
Lehman PV, Forsthuber T, Miller Aet al., Spreading of T cell autoimmunity to cryptic determinants of an antigen,Nature 358, 155–157 (1992).
Masuko K, Kato T, Ikeda Yet al., Dynamic changes of accumulated T cell clonotypes during antigenic stimulationin vitro andin vivo, Int Immunol 6, 1959–1966 (1994).
Choi Y, Lafferty JA, Clements JRet al., Selective expansion of T cells expressing Vβ2 in toxic shock syndrome,J Exp Med 172, 981–984 (1990).
Yamamoto K, Sakoda H, Nakajima Tet al., Accumulation of multiple T cell clonotypes in synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis,Int Immunol 4, 1219–1223 (1992).
Thomas R, McIlraith M, Davis LSet al., Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation,Arthritis Rheum 35, 1455–1465 (1992).
Sanders ME, Makgoba MW, Sharrow SOet al., Human memory T lymphocytes express increased levels of three adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-γ production,J Immunol 140, 1401–1407 (1988).
Akbar AN, Terry L, Timms Aet al., Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells,J Immunol 140, 2171–2178 (1988).
Jenkins MK, Pardoll DM, Mizuguchi Jet al., Molecular events in the induction of a nonresponsive state in interleukin 2-producing helper T-lymphocyte clones,Proc Natl Acad Sci USA 84, 5409–5413 (1987).
Quill H, Riley MP, Cho EAet al., Anergic Thl cells express altered levels of the protein tyrosine kinases p56lck and p59fynl,J Immunol 149, 2887–2893 (1992).
LaSalle J, Tolentino PJ, Freeman GJet al., Early signaling defects in human T cells anergized by T cell presentation of autoantigen,J Exp Med 176, 177–186 (1992).
Burns J, Littlefield KA, Role for antigen-presenting cells and bacterial superantigens in reversal of human T lymphocyte anergy,Eur J Immunol 23, 3300–3305 (1993).
Rellahan BL, Jones LA, Kruisbeek AMet al., In vivo induction of anergy in peripheral Vβ8+ T cells by staphylococcal enterotoxin B,J Exp Med 172 1091–1100 (1990).
Ignatowitcz L, Kappler J, Marrack P, The effects of chronic injection with superantigen-producing virus,J Exp Med 175, 917–923 (1992).
Gonzalo J, Moreno de Alboran Iet al., Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is an independent pathway of the interleukin-2 pathway,Eur J Immunol 22, 1007–1011 (1992).
Yamamoto K, Sakoda H, Nakajima Tet al., Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis,Int Immunol 4, 1219–1223 (1992).
Alam A, Lambert N, Lule Jet al., Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis,J Immunol 156, 3480–3485 (1996).
McCormack JE, Kappler J, Marrack P, Stimulation with specific antigen can block superantigen-mediated deletion of T cellsin vivo, Proc Natl Acad Sci USA 91, 2086–2090 (1994).
Author information
Authors and Affiliations
About this article
Cite this article
Miyata, M., Sekine, H., Sato, Y. et al. Selective expansion of large lymphoblasts expressing Vβ6.1-3 or 7 in synovial fluid from patients with rheumatoid arthritis. Japanese Journal of Rheumatology 8, 369–384 (1998). https://doi.org/10.1007/BF03041316
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03041316