The presumed hyporesponsive behavior of rheumatoid arthritis T lymphocytes can be attributed to spontaneous ex vivo apoptosis rather than defects in T cell receptor signaling

Journal of Immunology

Volumn 183, Issue 1, 2009, Pages 621-630

  Abreu, Joana R F ^a   Grabiec, Aleksander M ^a   Krausz, Sarah ^a   Spijker, René ^a   Burakowski, Tomasz ^b   Maslinski, Wlodzimierz ^b   Eldering, Eric ^a   Tak, Paul P ^a   Reedquist, Kris A ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b INSTITUTE OF RHEUMATOLOGY   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

CD28 ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 2; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; PROTEIN NOXA; T LYMPHOCYTE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; LYMPHOCYTE ANTIGEN RECEPTOR;

ADULT; AGED; APOPTOSIS; ARTICLE; BLOOD SAMPLING; CELL CULTURE; CELL ISOLATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DONOR; EX VIVO STUDY; FEMALE; HUMAN; HUMAN CELL; MALE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SYNOVIAL FLUID; T LYMPHOCYTE; COMPARATIVE STUDY; IMMUNOLOGY; METABOLISM; MIDDLE AGED; PATHOLOGY; PHYSIOLOGY; T LYMPHOCYTE SUBPOPULATION;

ADULT; AGED; AGED, 80 AND OVER; APOPTOSIS; ARTHRITIS, RHEUMATOID; CELL PROLIFERATION; CELLS, CULTURED; FEMALE; HUMANS; MALE; MIDDLE AGED; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; SYNOVIAL FLUID; T-LYMPHOCYTE SUBSETS;

EID: 68949116354     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0803278     Document Type: Article

References (61)

1. Lundy, S. K., S. Sarkar, L. A. Tesmer, and D. A. Fox. 2007. Cells of the synovium in rheumatoid arthritis-T lymphocytes. Arthritis. Res. Ther. 9: 202.
2. Firestein, G. S., and N. J. Zvaifler. 2002. How important are T cells in chronic rheumatoid synovitis? II. T cell-independent mechanisms from beginning to end. Arthritis. Rheum. 46: 298-308.
3. Clark, J., P. Vagenas, M. Panesar, and A. P. Cope. 2005. What does tumour necrosis factor excess do to the immune system long term? Ann. Rheum. Dis. 64(Suppl. 4): iv70 -iv76.
4. Malmstrom, V., C. Trollmo, and L. Klareskog. 2005. Modulating co-stimulation: a rational strategy in the treatment of rheumatoid arthritis? Arthritis Res. Ther. 7: S15-S20.
5. Winchester, R., E. Dwyer, and S. Rose. 1992. The genetic-basis of rheumatoidarthritis: the shared epitope hypothesis. Rheum. Dis. Clin. North Am. 18: 761-783.
6. de Vries, N., H. Tijssen, P. L. C. M. van Riel, and L. B. A. van de Putte. 2002. Reshaping the shared epitope hypothesis: HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67-74 of the HLADRB1 molecule. Arthritis Rheum. 46: 921-928.
7. Padyukov, L., C. Silva, P. Stolt, L. Alfredsson, and L. Klareskog. 2004. A geneenvironment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 50: 3085-3092.
8. Gourraud, P. A., J. F. Boyer, T. Barnetche, M. Abbal, A. Cambon-Thomsen, A. Cantagrel, and A. Constantin. 2006. New classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for rheumatoid arthritis structural severity. Arthritis Rheum. 54: 593-599.
9. van der Helm-van Mil, A. H. M., J. Z. Wesoly, and T. W. J. Huizinga. 2005. Understanding the genetic contribution to rheumatoid arthritis. Curr. Opin. Rheumatol. 17: 299-304.
10. Plenge, R. M., C. Cotsapas, L. Davies, A. L. Price, P. I. W. Bakker, J. Maller, I. Pe'er, N. P. Burtt, B. Blumenstiel, M. DeFelice, et al. 2007. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat. Genet. 39: 1477-1482.
11. Plenge, R. M., M. Seielstad, L. Padyukov, A. T. Lee, E. F. Remmers, B. Ding, A. Liew, H. Khalili, A. Chandrasekaran, L. R. L. Davies, et al. 2007. TRAF1-C5 as a risk locus for rheumatoid arthritis: a genomewide study. N. Engl. J. Med. 357: 1199-1209.
12. Raychaudhuri, S., E. F. Remmers, A. T. Lee, R. Hackett, C. Guiducci, N. P. Burtt, L. Gianniny, B. D. Korman, L. Padyukov, F. A. Kurreeman, et al. 2008. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat. Genet. 40: 1216-1223.
13. Moreland, L. W., R. Alten, B. F. Van den, T. Appelboom, M. Leon, P. Emery, S. Cohen, M. Luggen, W. Shergy, I. Nuamah, and J. C. Becker. 2002. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis. Rheum. 46: 1470-1479.
14. Kremer, J. M., R. Westhovens, M. Leon, E. Di Giorgio, R. Alten, S. Steinfeld, A. Russell, M. Dougados, P. Emery, I. F. Nuamah, et al. 2003. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. 349: 1907-1915.
15. Genovese, M. C., M. Schiff, M. Luggen, J. C. Becker, R. Aranda, J. Teng, T. Li, N. Schmidely, M. Le Bars, and M. Dougados. 2008. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann. Rheum. Dis. 67: 547-554.
16. + T-lymphocyte subsets in inflammatory rheumatic diseases. Am. J. Med. 84: 817-825.
17. Tak, P. P., R. Q. Hintzen, J. J. Teunissen, T. J. Smeets, M. R. Daha, R. A. van Lier, P. M. Kluin, A. E. Meinders, A. J. Swaak, and F. C. Breedveld. 1996. Expression of the activation antigen CD27 in rheumatoid arthritis. Clin. Immunol. Immunopathol. 80: 129-138.
18. Cush, J. J., and P. E. Lipsky. 1988. Phenotypic analysis of synovial tissue and peripheral blood lymphocytes isolated from patients with rheumatoid arthritis. Arthritis. Rheum. 31: 1230-1238.
19. Brennan, F. M., A. L. Hayes, C. J. Ciesielski, P. Green, B. M. Foxwell, and M. Feldmann. 2002. Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: involvement of phosphatidylinositol 3-kinase and nuclear factor B pathways in tumor necrosis factor α production in rheumatoid arthritis. Arthritis Rheum. 46: 31-41.
20. dim lymphocytes define populations of circulating effector cells that migrate to in-flamed tissues. Blood 109: 4328-4335.
21. Smeets, T. J., R. J. Dolhain, F. C. Breedveld, and P. P. Tak. 1998. Analysis of the cellular infiltrates and expression of cytokines in synovial tissue from patients with rheumatoid arthritis and reactive arthritis. J. Pathol. 186: 75-81.
22. Van der Graaff, W. L., A. P. Prins, T. M. Niers, B. A. Dijkmans, and R. A. van Lier. 1999. Quantitation of interferon γ- and interleukin-4- producing T cells in synovial fluid and peripheral blood of arthritis patients. Rheumatology 38: 214-220.
23. Isomaki, P., R. Luukkainen, O. Lassila, P. Toivanen, and J. Punnonen. 1999. Synovial fluid T cells from patients with rheumatoid arthritis are refractory to the T helper type 2 differentiation-inducing effects of interleukin-4. Immunology 96: 358-364.
24. +T cells in rheumatoid arthritis by flow cytometry. J. Rheumatol. 27: 1128-1135.
25. Combe, B., R. M. Pope, M. Fischbach, B. Darnell, S. Baron, and N. Talal. 1985. Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood. Clin. Exp. Immunol. 59: 520-528. (Pubitemid 15127600)
26. Firestein, G. S., and N. J. Zvaifler. 1987. Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis: II. Low levels of synovial fluid and synovial tissue interferon suggest that γ-interferon is not the primary macrophage activating factor. Arthritis. Rheum. 30: 864-871.
27. Firestein, G. S., W. D. Xu, K. Townsend, D. Broide, J. Alvaro-Gracia, A. Glasebrook, and N. J. Zvaifler. 1988. Cytokines in chronic inflammatory arthritis: I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J. Exp. Med. 168: 1573-1586.
28. Smeets, T. J., R. J. E. M. Dolhain, A. M. Miltenburg, R. de Kuiper, F. C. Breedveld, and P. P. Tak. 1998. Poor expression of T cell-derived cytokines and activation and proliferation markers in early rheumatoid synovial tissue. Clin. Immunol. Immunopathol. 88: 84-90.
29. Raza, K., F. Falciani, S. J. Curnow, E. J. Ross, C. Y. Lee, A. N. Akbar, J. M. Lord, C. Gordon, C. D. Buckley, and M. Salmon. 2005. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res. Ther. 7: R784-R795.
30. Cope, A. P., M. Londei, N. R. Chu, S. B. Cohen, M. J. Elliott, F. M. Brennan, R. N. Maini, and M. Feldmann. 1994. Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis. J. Clin. Invest. 94: 749-760.
31. Maurice, M. M., A. C. Lankester, A. C. Bezemer, M. F. Geertsma, P. P. Tak, F. C. Breedveld, R. A. van Lier, and C. L. Verweij. 1997. Defective TCR-mediated signaling in synovial T cells in rheumatoid arthritis. J. Immunol. 159: 2973-2978.
32. Maurice, M. M., H. Nakamura, E. A. van der Voort, A. I. van Vliet, F. J. Staal, P. P. Tak, F. C. Breedveld, and C. L. Verweij. 1997. Evidence for the role of an altered redox state in hyporesponsiveness of synovial T cells in rheumatoid arthritis. J. Immunol. 158: 1458-1465.
33. Isomaki, P., M. Panesar, A. Annenkov, J. M. Clark, B. M. Foxwell, Y. Chernajovsky, and A. P. Cope. 2001. Prolonged exposure of T cells to TNF down-regulates TCRζ and expression of the TCR/CD3 complex at the cell surface. J. Immunol. 166: 5495-5507.
34. Gringhuis, S. I., A. Leow, E. A. Papendrecht-van der Voort, P. H. Remans, F. C. Breedveld, and C. L. Verweij. 2000. Displacement of linker for activation of T cells from the plasma membrane due to redox balance alterations results in hyporesponsiveness of synovial fluid T lymphocytes in rheumatoid arthritis. J. Immunol. 164: 2170-2179.
35. Foey, A., P. Green, B. Foxwell, M. Feldmann, and F. Brennan. 2002. Cytokinestimulated T cells induce macrophage IL-10 production dependent on phosphatidylinositol 3-kinase and p70S6K: implications for rheumatoid arthritis. Arthritis Res. 4: 64-70.
36. Ziolkowska, M., A. Koc, G. Luszczykiewicz, K. Ksiezopolska-Pietrzak, E. Klimczak, H. Chwalinska-Sadowska, and W. Maslinski. 2000. High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J. Immunol. 164: 2832-2838. (Pubitemid 30115519)
37. Remans, P. H., C. A. Wijbrandts, M. E. Sanders, R. E. Toes, F. C. Breedveld, P. P. Tak, J. M. van Laar, and K. A. Reedquist. 2006. CTLA-4Ig suppresses reactive oxygen species by preventing synovial adherent cell-induced inactivation of Rap1, a Ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells. Arthritis Rheum. 54: 3135-3143.
38. Arnett, F. C., S. M. Edworthy, D. A. Bloch, D. J. McShane, J. F. Fries, N. S. Cooper, L. A. Healey, S. R. Kaplan, M. H. Liang, H. S. Luthra, et al. 1988. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 31: 315-324.
39. He, X., C. A. Janeway, M. Levine, E. Robinson, P. Preston-Hurlburt, C. Viret, and K. Bottomly. 2002. Dual receptor T cells extend the immune repertoire for foreign antigens. Nat. Immunol. 3: 127-134.
40. Eldering, E., C. A. Spek, H. L. Aberson, A. Grummels, I. A. Derks, A. F. de Vos, C. J. McElgunn, and J. P. Schouten. 2003. Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways. Nucleic Acids Res. 31: e153.
41. Salmon, M., D. Scheel-Toellner, A. P. Huissoon, D. Pilling, N. Shamsadeen, H. Hyde, A. D. D'Angeac, P. A. Bacon, P. Emery, and A. N. Akbar. 1997. Inhibition of T cell apoptosis in the rheumatoid synovium. J. Clin. Invest. 99: 439-446. (Pubitemid 27414801)
42. Maurice, M. M., E. A. van der Voort, A. Leow, N. Levarht, F. C. Breedveld, and C. L. Verweij. 1998. CD28 co-stimulation is intact and contributes to prolonged ex vivo survival of hyporesponsive synovial fluid T cells in rheumatoid arthritis. Eur. J. Immunol. 28: 1554-1562.
43. Alves, N. L., I. A. Derks, E. Berk, R. Spijker, R. A. van Lier, and E. Eldering. 2006. The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells. Immunity 24: 703-716.
44. Dzhagalov, I., A. Dunkle, and Y. W. He. 2008. The anti-apoptotic bcl-2 family member mcl-1 promotes T lymphocyte survival at multiple stages. J. Immunol. 181: 521-528.
45. Wojciechowski, S., P. Tripathi, T. Bourdeau, L. Acero, H. L. Grimes, J. D. Katz, F. D. Finkelman, and D. A. Hildeman. 2007. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J. Exp. Med. 204: 1665-1675.
46. Hughes, P. D., G. T. Belz, K. A. Fortner, R. C. Budd, A. Strasser, and P. Bouillet. 2008. Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity 28: 197-205.
47. Hutcheson, J., J. C. Scatizzi, A. M. Siddiqui, G. K. Haines III, T. Wu, Q. Z. Li, L. S. Davis, C. Mohan, and H. Perlman. 2008. Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity. Immunity 28: 206-217.
48. + T cell contraction. Immunity 28: 218-230.
49. Yamada, H., Y. Nakashima, K. Okazaki, T. Mawatari, J. I. Fukushi, N. Kaibara, A. Hori, Y. Iwamoto, and Y. Yoshikai. 2008. Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann. Rheum. Dis. 67: 1299-1304.
50. Chabaud, M., J. M. Durand, N. Buchs, F. Fossiez, G. Page, L. Frappart, and P. Miossec. 1999. Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 42: 963-970.
51. Kotake, S., N. Udagawa, N. Takahashi, K. Matsuzaki, K. Itoh, S. Ishiyama, S. Saito, K. Inoue, N. Kamatani, M. T. Gillespie, et al. 1999. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J. Clin. Invest. 103: 1345-1352.
52. Shahrara, S., Q. Huang, A. M. Mandelin, and R. M. Pope. 2008. TH-17 cells in rheumatoid arthritis. Arthritis Res. Ther. 10: R93.
53. Hirota, K., H. Yoshitomi, M. Hashimoto, S. Maeda, S. Teradaira, N. Sugimoto, T. Yamaguchi, T. Nomura, H. Ito, T. Nakamura, N. Sakaguchi, and S. Sakaguchi. 2007. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J. Exp. Med. 204: 2803-2812.
54. Sattler, A., U. Wagner, M. Rossol, J. Sieper, P. Wu, A. Krause, W. A. Schmidt, S. Radmer, S. Kohler, C. Romagnani, and A. Thiel. 2009. Cytokine-induced human IFN-gamma-secreting effector-memory Th cells in chronic autoimmune inflammation. Blood 113: 1948-1956.
55. Alves, N. L., R. A. W. van Lier, and E. Eldering. 2007. Withdrawal symptoms on display: Bcl-2 members under investigation. Trends Immunol. 28: 26-32.
56. Chen, L., S. N. Willis, A. Wei, B. J. Smith, J. I. Fletcher, M. G. Hinds, P. M. Colman, C. L. Day, J. M. Adams, and D. C. Huang. 2005. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell 17: 393-403.
57. Wu, L. X., J. La Rose, L. Chen, C. Neale, T. Mak, K. Okkenhaug, R. Wange, and R. Rottapel. 2005. CD28 regulates the translation of Bcl-xL via the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway. J. Immunol. 174: 180-194.
58. Hallaert, D. Y. H., R. Spijker, M. Jak, I. A. M. Derks, N. L. Alves, F. M. Wensveen, J. P. de Boer, D. de Jong, S. R. Green, M. H. J. van Oers, and E. Eldering. 2007. Crosstalk among Bcl-2 family members in B-CLL: seliciclib acts via the Mcl-1/Noxa axis and gradual exhaustion of Bcl-2 protection. Cell Death Differ. 14: 1958-1967.
59. + T cells. Blood 105: 1574-1581.
60. Azuma, M., H. Yssel, J. H. Phillips, H. Spits, and L. L. Lanier. 1993. Functional expression of B7/BB1 on activated T lymphocytes. J. Exp. Med. 177: 845-850. (Pubitemid 23104296)
61. Verwilghen, J., R. Lovis, M. De Boer, P. S. Linsley, G. K. Haines, A. E. Koch, and R. M. Pope. 1994. Expression of functional B7 and CTLA4 on rheumatoid synovial T cells. J. Immunol. 153: 1378-1385.